lectins, interconnecting proteins with biotechnological ...2. lectin induced mechanisms of...

Review ArticleLectins Interconnecting Proteins withBiotechnologicalPharmacological and Therapeutic Applications

Luana Cassandra Breitenbach Barroso Coelho1 Priscila Marcelino dos Santos Silva1

Vera Luacutecia de Menezes Lima1 Emmanuel Viana Pontual2 Patriacutecia Maria Guedes Paiva1

Thiago Henrique Napoleatildeo1 andMaria Tereza dos Santos Correia1

1Departamento de Bioquımica Centro de Biociencias Universidade Federal de Pernambuco Av Prof Moraes Rego 1235Cidade Universitaria 50670-901 Recife PE Brazil2Departamento de Morfologia e Fisiologia Animal Universidade Federal Rural de Pernambuco Rua DomManuel de Medeiros snDois Irmaos 52171-900 Recife PE Brazil

Correspondence should be addressed to Luana Cassandra Breitenbach Barroso Coelho lcbbcoelhogmailcom

Received 6 September 2016 Revised 21 January 2017 Accepted 6 February 2017 Published 7 March 2017

Academic Editor Omer Kucuk

Copyright copy 2017 Luana Cassandra Breitenbach Barroso Coelho et al This is an open access article distributed under the CreativeCommons Attribution License which permits unrestricted use distribution and reproduction in any medium provided theoriginal work is properly cited

Lectins are proteins extensively used in biomedical applications with property to recognize carbohydrates through carbohydrate-binding sites which identify glycans attached to cell surfaces glycoconjugates or free sugars detecting abnormal cells andbiomarkers related to diseases These lectin abilities promoted interesting results in experimental treatments of immunologicaldiseases wounds and cancer Lectins obtained from virus microorganisms algae animals and plants were reported asmodulatorsand tool markers in vivo and in vitro these molecules also play a role in the induction of mitosis and immune responsescontributing for resolution of infections and inflammations Lectins revealed healing effect through induction of reepithelializationand cicatrization of wounds Some lectins have been efficient agents against virus fungi bacteria and helminths at lowconcentrations Lectin-mediated bioadhesion has been an interesting characteristic for development of drug delivery systemsLectin histochemistry and lectin-based biosensors are useful to detect transformed tissues and biomarkers related to diseaseoccurrence antitumor lectins reported are promising for cancer therapy Here we address lectins from distinct sources with somebiological effect and biotechnological potential in the diagnosis and therapeutic of diseases highlighting many advances in thisgrowing field

1 Introduction

Considering the diverse diseases and infectious agents thataffect the human species and their consequences the biotech-nological field has searched biorecognition molecules fromnatural or recombinant sources with diagnostic and thera-peutic potential The key for efficient detection treatmentand healing of pathological conditions is the biorecognitionevent The identification of carbohydrate moieties in cellsurface and glycoconjugates has been performed with the useof lectins a heterogeneous group of proteins (or glycopro-teins) of nonimmune origin that bind carbohydrates throughmolecular sites with high affinity and specificity [1] Theseparticular lectin sites interact withmono- or oligosaccharides

through no covalent linkage involving hydrogen bonds vander Walls and hydrophobic interactions with reversibilityhigh specificity and no catalytic or immune activity [2 3]Lectins have been isolated from distinct sources such asviruses bacteria fungi algae animals and plants [1] theyshow specificity to distinct carbohydrates such as man-nose sialic acid fucose N-acetylglucosamine galactoseN-acetylgalactosamine complex glycans and glycoproteins [45] Lectins recognize carbohydrates and glycoconjugates incells tissue sections and biological fluids being valuabletools in biotechnology including diagnosis and pharmaco-logical and therapeutic applications [6ndash8]

Some lectins mediate the infection mechanism throughthe interaction of viral lectins with glycan chains on surface of

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2017 Article ID 1594074 22 pageshttpsdoiorg10115520171594074

2 Evidence-Based Complementary and Alternative Medicine

T cell

Lectin

Mitogenicactivation

Receptor

(a)

T cell Naive CD4+

Th 1

Th 2

Th 17

CD8 T cell

NK cell

Macrophage

Eosinophil

B cell

Mast cell

Tissue immunity

(b)

Figure 1 Lectins induced in vitro mitogenic activation of T cells (a) and stimulated in vivoTh1 Th2 andTh17 responses (b)

host cells resulting in the virus entrance into cell [30] Sialicacid-specific lectins such as influenza virus hemagglutininwere used to search antiviral drugs and inhibitors that canremove or block the sialic acid site in host cells in orderto prevent the binding [31] Lectins from bacteria play arole in the bacterial virulence through the binding betweenbacterial lectins and specific carbohydrate moieties of hostcells being an important factor for recognition and adhesion[32 33] Strong anti-HIV (human immunodeficiency virus)activity in vitro has been described to bacterial lectins [34ndash36] Various fungal lectins distributed among mushroomsmicrofungi and yeasts exhibited many physiological effectsand biomedical applications Similar to bacterial lectins theinteraction between fungal lectins and host glycans has animportant role in the infection process of fungi [37] Fungallectins revealed immunomodulatory mitogenic antiprolif-erative antitumoral antiviral and antimicrobial activities[5 38]

A large number of algal lectins have also attractedconsiderable attention for biomedical applications includinganti-HIV antitumoral antimicrobial anti-inflammatory andantinociceptive activities [39] Animal lectins play a rolein various physiological processes such as metastasis ofcancer apoptosis pathways and immunomodulation [40 41]Many lectins isolated from animal tissues were investigatedas apoptotic agents immunomodulatory antiviral therapyand anticancer drug targets [41 42] Plant lectins purifiedand characterized from distinct plant families and tissuesincluding seeds barks leaves roots fruits and flowersexhibited various molecular features structures and carbo-hydrate specificities [43] The Leguminosae family has thelargest group of well-characterized legume lectins which areinteresting due to a variety of carbohydrate specificity andgreater availability in nature [44] In general a wide rangeof biological applications has been attributed to plant lectinssuch as mediators of inflammatory and immune responseantiviral antibacterial antifungal and antihelminthic agentshealing effect drug delivery histochemical markers biosens-ing of diseases and antitumoral activities [3 45 46] Thisreview discusses representative lectins from distinct naturalsources highlighting some biological effects in vivo andin vitro and their potential for diagnosis and therapeuticapplications

2 Lectin Induced Mechanisms ofImmunological and InflammatoryResponses

Immunological and inflammatory responses play a role inthe protection of an organism against an invasive agentand transformed cells The immune system acts throughtwo ways known as innate and adaptive immune responsesactivated by a group of cells and molecules that promotethe inactivation or destruction of aggressive agent [47]There are neutrophils eosinophils basophils and mono-cytesmacrophages with specific functions and ability toproduce and release molecules named cytokines whichmodulate the activation of immune cells inflammation andhumoral response The search for biomolecules that canmodulate (up or down) mechanisms of immune responseis attractive for adjustment of immune conditions andtherapeutic applications in diverse immune response-relateddiseases and infections

Several lectins from distinct sources showed immuno-modulatory effects such as mitogenic activity (Figure 1(a))and induction of T helper type 1 (Th1) type 2 (Th2) ortype 17 (Th17) responses (Figure 1(b)) The pivotal step tostart immunomodulatory activities of lectins is the binding oflectins to glycans targets on cell surface which have the role oflectin-receptors [48] Lectin binding can induce the immuneresponse through mediators such as second messengersreleased from themembrane For example diacylglycerol andinositol 145-triphosphate generated through the hydrolysisof phosphatidylinositol 45-diphosphate increase in cytoso-lic Ca2+ levels release of cytokines specifics binding toreceptors distributed in stimulatory regions or domainscascade started by linkage to TCR receptor and further othermechanisms incompletely elucidated [49 50]

Fungal lectins have been highlighted as potent modu-lators of immune response TML-1 and TML-2 are lectinsfrom the mushroom Tricholoma mongolicum which inducedthe Th1 response through the activation of macrophagesfrom lectin-treated mice and stimulated the production ofnitrite ion and cytokine tumor necrosis factor (TNF) bymacrophages Additionally both lectins promoted in vivoactivation of mouse macrophages triggering the inhibitionof tumor cell growth [51] These effects may result from

Evidence-Based Complementary and Alternative Medicine 3

the lectin binding to the glycan determinants on mousemacrophages surface modulating the immune responseA lectin purified from the edible mushroom Volvariellavolvacea named VVL induced the proliferation of murinesplenic lymphocytes and stimulated the transcriptionalexpression of interleukin 2 (IL-2) and interferon 120574 (INF120574) invitro stimulating the Th1 response [52] Similar activity wasevidenced by a mushroom lectin from Ganoderma capensewhich induced high proliferative response in mouse spleno-cytes [53]The lectin isolated from another edible mushroomPleurotus citrinopileatus showed in vitro mitogenic activityon mouse splenocytes with the maximal stimulation at 2 120583Mof lectin concentration [54] These lectins could have somesimilarity with fungal immunomodulatory proteins such asFip-vvo in the slight N-terminal sequence which may berelated to this proliferative response [52 53]

Immunomodulatory activities of Agaricus bisporus lectin(ABL) from edible mushroom acted on innate and adap-tive immune responses in vivo and in vitro but showedan inhibitory and antiproliferative effect on macrophagesABL downregulated in vitro nitric oxide (NO) productionby mouse peritoneal macrophages after lipopolysaccharidestimuli and inhibited mononuclear cell proliferation underdifferent conditions Orally administered ABL to BALBcmice also induced inhibition of NO production by peritonealmacrophages and stimulated a tumor development Theinteraction ofABL-macrophages occurs through the terminalresidues of T antigen and sialyl-T antigen in mucin-typeO-glycans exposed on macrophages and this interactioncan modify the Akt signaling pathway ABL binding canblock Akt phosphorylation resulting in the inhibition ofNO production and cytokine production by macrophages[55] Unlike this the oral treatment with ABL promoted areduction of the tumor growth and attenuated symptoms ofexperimental autoimmune encephalomyelitis in Wistar rats[55]

A mycelial lectin from Aspergillus nidulans microfungiinduced an increase of NO production and IFN120574 and IL-6levels also enhanced in splenocyte cultures from treated Swissalbino mice groups Additionally the lectin promoted anantianaphylactic effect and preventedArthus reaction in vivoa therapeutic potential against ulcerative colitis was observedin rats pretreated with the lectin via intraperitoneal injectionthat showed better recovery comparing with posttreated ratsThe high specificity of this lectin for N-acetylgalactosamine(GalNAc) residues on epithelial cells could trigger the thera-peutic effect [56]

Seaweed lectins are widely studied due to attractivebiological activities The mitogenic activity for T lympho-cytes from mouse spleen was firstly reported to a lectinfrom the red seaweed Carpopeltis flabellate (Carnin) [57]The lectin from green seaweed Caulerpa cupressoides (CcL)showed antinociceptive and anti-inflammatory activities onzymosan-induced arthritis in rat temporomandibular jointRats treated with CcL reduced until 895 zymosan-inducedhypernociception and leukocyte influx until 985 Thelectin also lowers the expression levels of IL-1120573 and TNF120572compared with nontreated group being a probable way for

antinociception and anti-inflammation effects lectin induced[58]

Animal lectins present in different tissues from insectsfishes and mammalians among others play importantroles in immune system regulation being applied as potentimmunomodulators Mitogenic activity was reported to a D-galactose-binding lectin fromMusca domestica pupae Prolif-eration of mouse splenocytes was stimulated in the presenceof the lectin in vitro with maximal activity at a concentrationof 20120583gmL [59] A rhamnose-specific lectin isolated fromovaries of the grass carp fish (Ctenopharyngodon idellus)showed immunostimulatory effect including proliferativeresponse inmurine splenocytes and peritoneal exudates cellsGrass carp lectin also induced IL-2 and IFN120574 expressionin treated splenocytes [60] A lectin also was isolated fromroe of the grass carp and similarly to lectin from grass carpovaries showedmitogenic activity onmurine splenocytes andstimulated the phagocytic activity of sea breammacrophages[61] A mannose-binding lectin from the ovary of cobia fish(Rachycentron canadum) also exhibited mitogenic activity onmouse splenocytes at 14 120583M [62] Another mannose-bindinglectin isolated from serum of cobia named Rachycentroncanadum lectin (RcaL) was also reported as immunomodu-latory agent The mitogenic response and cytokine produc-tion in splenocytes from mice in vitro treated with RcaLwere evaluated A high proliferation index to treated cells andinduction of high levels of IL-2 and IL-6 production wereobserved RcaL was a potential mitogenic agent [63] RcaLinducedTh 1 response in treated cultures of mice splenocytesthrough IFN-120574 and NO production without cytotoxicity[64] A mannose-specific lectin from serum of Oreochromisniloticus (Nile tilapia fish) denominated OniL demonstratedin vitro Th1 response induction on mice splenocytes OniLalso stimulated high levels of IFN120574 production and low levelsof IL-10 and nitrite without cytotoxic effect [65]

Galectins are a family of 120573-galactoside-binding lectinsoccurring in animals and play important roles in diverseimmunomodulatory processes Galectin-1 revealed a regula-tory role in the thymocytematuration through the interactionwith O-glycans on immature cortical thymocyte surface[66] In addition galectin-1 induced apoptosis of immaturethymocytes by activation of a p53 pathway [67] and inhibitedcell growth as observed to human leukemia T cells [68] Itis suggested that galectin-1 induced apoptosis through theregulation of intracellular signals such as activation of AP-1transcription factor downregulation of Bcl-2 and activationof caspases [69] Galectin-3 behaved as a mitogenic and anti-apoptotic agent on human leukemia T cells with apoptosisinduced by Fas receptor ligation and by staurosporine [70]The high sequence similarity of galectin-3 with an antiapop-totic protein family named Bcl-2 including the presenceof the NWGR motif highly conserved in Bcl-2 suggeststhat galectin-3 can modulate the Bcl-2 pathway and inhibitapoptosis [70] Galectin-3 also prevents the apoptosis byprotection of the mitochondrial membrane and inhibition ofreactive oxygen species production [69] Moreover galectin-3 acts as a chemotactic agent to monocytes and macrophagesby a G-protein pathway [69]


A group of C-type lectins known as macrophage gal-actose-type lectin (MGL) are commonly glycan-bindingreceptors on dendritic cells and macrophages from humanimmune system that participate in immune response stepsas pathogen recognition endocytosis and presentation ofantigens to T cells In the activation of human T cellsMGL recognize Tn antigens on the CD45 of effector T cellstriggering reduction in the phosphatase activity of CD45inhibition of T cell proliferation and inflammatory cytokinesproduction and T cell apoptosis [71] Human MGL canenhance IL-10 production by dendritic cells and induce theproliferation of regulatory T cells and CD8+ T cell responses[71]

Many mechanisms of immunomodulation have beenattributed to plant lectins Phytohemagglutinin (PHA) is anN-acetylgalactosamine specific lectin from red kidney bean(Phaseolus vulgaris) and one of the first lectins identifiedas mitogenic agent to lymphocytes [72] Concanavalin A(Con A) is a mannoseglucose specific lectin isolated fromCanavalia ensiformis seeds and is among some lectins usedas models in lectin-carbohydrate interaction studies Con Ahas been reported as mitogenic agent on CD4+ T cells andas antitumoral Autophagic pathway induced by Con A isbeginning when the lectin binds to the mannose residues onthe cell membrane internalized through clathrin-mediatedendocytosis to the mitochondria altering its membrane per-meability and inducing themitochondria autophagy tumoralcells suffer the cell death [73] Con A is commonly usedas positive control in the evaluation of immunomodulationinvolving other lectins

Immunomodulatory activity reported to Korean mistle-toe (Viscum album) lectin (KML) showed a stimulatory effecton expression of cytokines IL-3 IL-23 and TNF120572 and in theintracellular reactive oxygen species (ROS) generation whileinhibiting events induced by lipopolysacharride such as theproduction of IL-10 and NO [74] Agglutinin from Abrusprecatorius has been reported as an inductor of Th1 immuneresponse through splenocyte activation and induction of IL-2 IFN120574 and TNF120572120573 cytokine production Native and dena-tured forms of A precatorius agglutinin [75] also inducedNK-cell activation and thymocyte proliferation ConBr amannose-binding lectin from Canavalia brasiliensis seedsdemonstrated mitogenic activity on in vitro splenocytesshowed upregulation in the IL-2 IL-6 and IFN120574 expressionand a decrease in IL-10 expression [76]

Isoforms of mannose-binding lectins purified fromCratylia mollis leguminous seeds Cramoll 1 and Cramoll14 demonstrated high potential to stimulate human Tlymphocyte mitogen in vitro [77] Cramoll 14 and ConA also showed high mitogenic activity in vivo in spleno-cytes from mice previously inoculated and were potentialinductors of cytokines IL-2 IL-6 and IFN120574 release as wellas NO production stimulating the Th1 response [78] It issuggested that its mitogenic activity on T lymphocytes isinduced by transmembrane signals started with the Cramollbinding to glycans of the cell surface and the proliferation ofsplenocytesmay be induced by a TCR-dependentmechanism[78] Another study reported the potential of Cramoll 14 tostimulate rat spleen lymphocytes activation in vivo through

a significant increase of cytosolic Ca2+ and ROS Cramoll 14-induced In this case the production of ROS may be inducedby NADPH oxidase and to have relation with the increase ofCa2+ release Cramoll 14 also promoted an increase in IL-1120573levels and stimulated the Th2 response [79] Immunomodu-latory activity of Cramoll 14 Con A and PHA was demon-strated in experimental cultures of treated mice lymphocytesby the induction of Th1 response showing NO suppressionhigh production of IFN120574 low production of IL-10 andanti-inflammatory activity [80] Cramoll 14 also stimulatedcytokine releases in Th 17 pathway inducing the productionof IL-6 IL-17A IL-22 and IL-23 as well as immunologicmemory in cultured splenocytes [81] Immunomodulatoryeffects of Cramoll 14 and recombinant Cramoll (rCramoll)were observed on cell culture of mice peritoneal exudatesinfected and noninfected with Staphylococcus aureus Thelectins induced the production of IL-1120573 and IFN120574 reducingthe expression of TNF120572 and IL-6 in S aureus infected cellsNO and ROS production enhanced and phagocytic activityof S aureus increased Both lectins stimulate phagocyticactivity and production of proinflammatory cytokines byactivation of intracellular signaling cascades [82]

A lectin purified from taro (Colocasia esculenta) thetarin promoted proliferation of mouse splenocytes in vitroand in vivo Optimum in vitro cellular proliferation wasobserved in mouse splenocytes treated with 500 ng of tarinand total in vivo proliferationwas 33-fold higher than controlgroup [83] A lectin from Ziziphus oenoplia RhamnaceaeZ oenoplia seed lectin (ZOSL) showed potential antialler-gic and anti-inflammatory effects by prevention of Arthusreaction and anaphylactic shock in vivo in Wistar albinorats after oral administration of ZOSL (200mgkg of bw)[84]

Some lectins isolated from edible tissues of plants haveimmunomodulatory activity Garlic (Allium sativum) lectinsASA I and ASA II revealed a mitogenic effect in humanperipheral blood lymphocytes murine splenocytes and thy-mocytes and stimulated in vitro histamine release fromleukocytes in atopic patients when compared with nonatopicindividuals [85] A mannose-specific lectin from onion(Allium cepa agglutinin ACA) also showedmitogenic activityin murine thymocytes as well as a high production of IFN120574and IL-2 An increase in the release of NO and in the pro-duction of cytokines TNF120572 and IL-12 by murine macrophagecell line (RAW2647) and rat peritoneal macrophages wasobserved after 24 h of the lectin treatment showing aninductor effect on Th1-type immune response in vitro [86]Banana (Musa acuminata) lectin (BanLec) showed in vivoimmunomodulatory effect BanLec was orally administeredtomice and after seven days mouse peripheral blood showedan increased level in IL-10 IL-17 and TNF120572 and a reductionof IL-6 and IFN120574 In addition CD4+ T cells enhancedwhile the CD8+ T cell population reduced in mouse thymus[87]

These findings show the importance of lectin-basedrecognitions to regulate inflammatory processes and immuneresponses with their potential for biotechnological applica-tions to understand immune mechanisms and therapeutictools for immunological disorders and diseases


3 Antifungal and AntiparasiticActivities of Lectins

Recent studies have demonstrated the potential of lectinsfrom different origin and carbohydrate specificities as anti-fungal and antiparasitic agents Plant lectins investigatedfor antifungal potential mainly against phytopathogenicspecies have most reported antifungal effects binding tohyphae causing inhibition of growth and prevention of sporegermination For example a lectin isolated from Myracro-druon urundeuva heartwood was able to inhibit in morethan 50 the mycelial growth of Fusarium oxysporum Fdecemcellulare and F fusarioides [26] Fusarium growth wasalso impaired by a galactose-specific lectin isolated fromBauhiniamonandra secondary roots with highest effect (30inhibition) on F solani [45] Inhibitory effects of lectinson growth of phytopathogens from other genera were alsoreported Lectins from Phaseolus vulgaris seeds inhibitedthe growth of Coprinus comatus and Rhizoctonia solani [88]as well as Valsa mali [89] A mannan-specific lectin fromOphioglossum pedunculosum roots strongly damaged thegrowth of Sclerotium rolfsii at 40 120583gmL [90]

Microgramma vacciniifolia rhizome lectin had its carbo-hydrate-binding ability inhibited by glycosylated moleculesfrom F oxysporum f sp lycopersici mycelia [91] Theseauthors then suggested that the interaction between thislectin and fungal carbohydrates might be involved in thegrowth inhibitory property detected against races 1 2 and3 of this phytopathogen However the carbohydrate-bindingsites of lectins are not always involved in the antifungal actionAn example is the lectin from Astragalus mongholicus rootswhich was active against F oxysporum Colletotrichum spDrechslera turcia andmainlyBotrytis cinereaThe addition oflactose and galactose (inhibitors of hemagglutinating activityof this lectin) in the assay did not interfere with antifungaleffect [92]

A chitin-binding lectin from Setcreasea purpurea rhizomeinhibited the germination of R solani Sclerotinia sclero-tiorum Penicillium italicum and Helminthosporium maydisspores with minimal inhibitory concentrations ranging from481 to 962120583gmL [93] In the sameway jackin and frutackintwo chitin-binding lectins from the genus Artocarpus inhib-ited the germination of Fusarium moniliforme spores at aconcentration of 225mgmL [94]The authors of both worksalso reported that these lectins impaired the development ofhyphae the mycelia formed were not able to produce sporesand the chitin-binding property is probably involved in thefungistatic action Interestingly the antifungal property ofS purpurea lectin remained even after heat-treatment of theprotein at 75∘C [93]

Antifungal lectins have specificity regarding fungalspecies mannoseglucose-binding lectin from Capsium fru-tescens var fasciculatum seeds was able to inhibit the sporegermination and hyphal growth of Aspergillus flavus andFusarium moniliforme but showed no effect on F gramin-earum F solani Physalospora piricola and B cinerea [95]

Some plant lectins were used in plant transgenic re-searches this is the case of lunatin a glycosylated and met-al-dependent lectin isolated from Phaseolus lunatus seeds

which showed potent antifungal activity against Sclerotiumrolfsii P piricola F oxysporum and B cinerea [96] Anotherexample is the lectin from rhizome of Ophiopogon japon-icus with antifungal activity against Gibberella saubinetiiand R solani showing minimal inhibitory concentra-tions of 006 and 005mgmL respectively This lectin isable to interact with glycans containing mannose [Man-120572(1316)-mannotriose Man-120572(13)-Man Man-120572(16)-ManMan-120572(12)-Man Me120572-D-man and D-mannose] and itscarbohydrate-binding sites shown to be very structurallysimilar to those frommonocot lectins [97] Transgenic plantsexpressing antifungal lectins were already effectively devel-oped and tested under laboratory conditions Transgenicrice plants expressing a stable monomeric mutant variant ofAllium sativum leaf lectin exhibited reduced sensitiveness tosheath blight disease caused by R solani in comparison withnontransformed plants [98]

Fungi that are human and animal pathogens are alsoaffected by antifungal lectins Helianthus annuus seed lectininhibited the growth and altered membrane permeability ofCandida tropicalis Candida parapsilosis Candida albicansand Pichia membranifaciens This protein was also able toinduce the formation of pseudohyphae and the production ofreactive oxygen species in C tropicalis [99] A lectin isolatedfrom Cladonia verticillaris lichen was able to inhibit thegrowth (35) of dermatophyte Trichophyton mentagrophytes[100] Klafke et al [101] evaluated the potential of Con Aand Abelmoschus esculentus Mucuna pruriens and Clitoriafairchildiana lectins against Candida albicans C tropicalisC parapsilosis Cryptococcus gattii Cryptococcus neoformansMalassezia pachydermatis Rhodotorula sp and Trichosporonsp however only C parapsilosis growth was inhibited bythese lectins Pinheiro et al [102] reported antifungal effectof Talisia esculenta lectin on arthroconidial forms of thedermatophyte Microsporum canis obtained from hairs ofinfected animals Authors proved that the antifungal mecha-nism involved the carbohydrate-binding sites of this protein

Antifungal lectins obtained from other organisms suchas the mussel Crenomytilus grayanus contain a lectin ableto inhibit germination of conidia from several Aspergillusstrains [103] A galactoseN-acetylgalactosamine-specificlectin from the mussel Mytilus trossulus impaired conidiagermination of species belonging to Fusarium TrichodermaHaematonectriaAspergillus andAlternaria genera [103 104]

The relationship between structure and antifungal activ-ity of lectins is also target of researches The lectin from theplantPinellia ternata f angustata contains two domains calledPTADOM1 and PTA-DOM2 each one with a mannose-binding site This lectin as well as the two separate domains(expressed in Escherichia coli) showed antifungal activitytoward the phytopathogensAlternaria alternata andBipolarissorokiniana and the dermatophyte Curvularia lunata Thewhole lectin showed higher activity than two separateddomains an expected result since both domains exert anti-fungal action [105]

The effects of lectins on human and animal parasitesinvestigated under different approaches include the deter-mination of parasiticidal action prevention of infectionand study of the involvement from carbohydrate-receptor


interactions on the infective process The lectins Con Aand ricin promoted tegumental damage (basal vacuolationand swelling of the basal membrane invaginations) in adultworms of Schistosoma mansoni (schistosomiasis causer)which were prevented when assays were performed in pres-ence of carbohydrates that inhibit these lectins [106] ConA Triticum vulgaris and Glycine max lectins interferedwith migration pattern of Strongyloides ratti (rat thread-worm) along a sodium chloride gradient which indicates theinvolvement of carbohydrate moieties in the chemosensoryactivity of labial sensilla in this nematode [107] Lectins fromCoprinopsis cinerea Aleuria aurantia and Laccaria bicolorshowed larvistatic effect on Haemonchus contortus (Barberrsquospole worm) resulting in arresting at L1 phase the lectin fromMarasmius oreades promoted larval death [108] Cramoll 14was evaluated for in vivo antihelminthic activity using miceinfected with S mansoni the treatment with this lectin ledto decrease in the number of excreted eggs recovered adultworms and liver granulomas [109]

Plant lectins prevented the infection of intestinal epithe-lium of Psetta maxima fish by the myxozoan Enteromyxumscophthalmi Con A and Glycine max lectins inhibitedattachment and invasion of E scophthalmi to the intestinalepithelium authors suggested that these lectins acted byblockingN-acetylgalactosamine galactose mannose andorglucose residues that are important in the interaction betweenthe parasite and intestinal cells [22] A lectin isolated fromSynadenium carinatum latex reduced the infection of murinemacrophages by Leishmania amazonensis [110] Authors alsoreported that the lectin showed no cytotoxicity to mam-malian host cells and that the macrophages treated with thelectin showed increased expression of cytokines IL-12 IL-1and TNF120572

Lectins also evaluated the use in control of host andvectors from parasites and virus The Microgramma vaccini-ifolia rhizome lectin at 100 120583gmL was able to promote deathof Biomphalaria glabrata (intermediate host of S mansoni)embryos and adults in addition the snails treated with thelectin laid a fewnumber of eggs amongwhich several showedmalformations [111] The lectins from Cratylia floribunda(CFL) and Dioclea guianensis (Dgui) were also able to pro-mote death of B glabrata adult snails [112] Larvicidal activityof lectins from Myracrodruon urundeuva bark heartwoodand leaves against the mosquito Aedes aegypti (vector ofthe virus that causes dengue fever chikungunya and zikavirus fever) was reported [113 114] In addition lectinsisolated from whole seeds and seed cake of Moringa oleiferademonstrated larvicidal ovicidal and oviposition-stimulanteffects on A aegypti being considered important candidatesfor using in control of mosquito population including intraps for egg capture [115ndash118]

4 Lectins for Healing Applications

Many researchers have reported healing effect induced bylectins The healing is the process of tissue repair aftertrauma in which a monitored group of cells and moleculestrigger ordered phases to result in anatomical and functionalrestoration of injured tissues [119] The repair in response to

injury includes sequential phases of hemostasis inflamma-tory phase tissue formation (proliferation) and remodelingof extracellular matrix (tissue maturation) Firstly coagu-lation factors and platelets promote the blood coagulationin the damaged tissue Inflammatory cells as neutrophilsand macrophages phagocyte damaged cells and extracellularmatrix thus a new tissue starts its regeneration and finallythe scar formation [120] The role of lectins as healing agentsis not completely clear however lectins may influence theimmune response production of cytokines inflammatoryresponse and cell antiproliferative effect during the healingprocess [8] Lectins have promoted healing effect in cuta-neous wounds and modification of scarring process withgreat results and therapeutic potential

Antiproliferative effect of an edible mushroom Agaricusbisporus lectin (ABL) in a model of wound healing wasevaluated on human ocular fibroblasts in vitro in order totest the control of scar formation [121] Ocular fibroblastproliferation was inhibited until 40 and collagen latticecontraction was completely abolished at 100 120583gmL of ABLThese effects indicate the potential of ABL to modulate thehealing process and scar formation in human ocular tissueABL may inhibit the proliferation by the influence of growthfactors as epidermal growth factor and insulin It was alsoproposed that ABL is internalized after the linkage andaccumulates around the nucleus where it may block nuclearlocalizing sequence- (NLS-) dependent uptake of protein intothe nucleus [121 122]

A lectin isolated from themarine red algae Bryothamnionseaforthii (BSL) demonstrated prohealing potential on skinwounds in mice [123] Induced wounds in dorsal thoracicregion of mice were submitted to topical treatment with BSLDuring the treatment BSL showed proinflammatory effectand stimulated reduction of the wound areas After 7 and 12days treatment with BSL promoted the synthesis of collagenby fibroblasts and active presence of young skin annexespromoting the restructuration of the luminal epithelium andan effective wound closure Here BSL plays an immunomod-ulatory effect on immune cells during inflammatory andproliferative phases where BSL demonstrated stimulatoryactivity on the migration of polymorphonuclear cells toinjured site and activation of fibroblasts resulting in theprohealing effect [123]

Galectins 3 and 7 play important role in reepithelializa-tion of wounds according to study conducted in modelsof mice corneal wound healing [124] Significant reductionin reepithelialization of wounds was observed in galectin 3-deficient (gal3minusminus) mice lineage when compared with wild-type lineage (gal3++) In the in vitro healing assay thepresence of galectin-3 stimulated reepithelialization of corneawounds in gal3++ lineage but not in gal3minusminus probably dueto its deficiency of galectin 7 On the other hand galectin 7induced reepithelialization of cornea wounds in gal3minusminus andgal3++ These results represent a potential application of gal3and gal7 for treatment of woundsMembers of galectin familyhave showed possibility ofmediating cell-matrix interactionsmainly galectin 3 which has been expressed in inflammatorycells and fibroblasts and located at sites of corneal epithelial


cell-matrix adhesion and may stimulate cell-matrix interac-tion and cell migration in the wound healing process [124]

Mannose-binding lectin (MBL) replacement therapy wasreported as a healing strategy of a radiation-induced chroniculcer [125] In this study a patient with an insufficient level ofMBL and a chronic radiation-induced ulcer after treatmentof breast cancer was observed which even after 15 monthsof conservative treatment and plastic surgery a satisfactoryhealing was not obtainedThus an experimental intravenoustherapy with human plasma-derivedMBLwas carried out for6 weeks after the treatment a complete healing was obtainedMBL is a component of innate immunity and its role in theelimination of microorganisms and modulation of immuneresponse could contribute to wound healing

D-mannose-binding lectin from Artocarpus integrifolia(jackfruit) seeds known as KM+ or artocarpin promotedwound healing on rabbit corneal epithelium [126] Firstlylesion of 60mm diameter area was induced on the corneaof both eyes of experimental and control groups The lesionsof groups were treated with KM+ and buffer respectively thewound areas were monitored by fluorescein staining KM+enhanced the neutrophil influx into the wound area andmay stimulate the production of cytokines contributing forcorneal epithelium healing [126]

Prohealing potential on skin wounds in mice was showedby the native lectin of orchid tree Bauhinia variegata (nBVL)and its recombinant isoform (rBVL-1) [127] Dorsal skinwounds were induced surgically in mice followed by topicallectin treatment for 12 days Both lectins promoted woundclosure in treated animals and all skin layers were restruc-tured It is suggested that the prohealing effects of nBVL andrBVL-1 are due to stimulatory potential of these lectins formitosis of resident cells such as macrophages and mast cellstriggering the release of cytokines and the recruitment ofneutrophils into the wound areaThese prohealing propertiesare attractive for therapy applications involving skin wounds

Cramoll 14 has been reported as healing agent [8]In order to analyze the cicatricial power the lectin wasapplied to topical treatment of cutaneous wounds surgicallyinduced in normal and immunocompromised albino Swissmice [128] Treated animals showed more edema formationand recruitment of more polymorphonuclear cells at thewoundsThe prevalence of polymorphonuclear cells inducedby Cramoll 14 is important to remove cell debris andmicroorganisms in the wound favoring the healing [128]Cramoll 14 also induced efficiently the granulation phasecollagen fiber deposition and no incidence of microorgan-isms in all treated wounds resulting in wound closure andrepair faster than control groups A parallel study conductedin female albino Swiss mice with skin wound surgicallyinduced included daily treatment with Cramoll 14 (5 and10 120583g100 120583l) at 2nd 7th and 12th days Macroscopic andhistological aspects of treated groups were compared witha positive control group treated with Con A (10 120583g100 120583l)and a negative control group administered with 150mMNaCl In the 12th day wound closure complete reepithe-lialization a great deposition and organization of collagenfibers and formation of cutaneous annexes were observed inwounds treated with lectins no wound closure and partial

reepithelialization were visualized in negative control group(Figure 2) Another study related the occurrence of gradualhealing process induced by a hydrogel containing Cramoll 14on experimental second-degree burns in rats [129] On the7th day of treatment treated group showed higher edemaexudates and necrosis With more 7 days tissue reepithe-lialization and moderate autolysis were observed With moretwo weeks tissue epithelialization was completed and inthe 35th day was observed a modeled dense collagen Thepotential for healing of cutaneous wounds and thermal burnshas been related to immunomodulatory profile of Cramoll 14described in other studies including proinflammatory actionin polymorphonuclear cells induction of cytokines releaseand proliferation of fibroblasts

A lectin from Eugenia malaccensis seeds (EmaL) inducedhealing of cutaneous wounds in mice [130] Surgical woundsproduced in the skin followed by daily treatment with topicaladministration of EmaL reduced the intensity of inflamma-tory signals such as edema and hyperemia However higherreepithelialization with well-organized collagen fibers thancontrol group was observed EmaL was efficient to inducethe repairing of cutaneous wounds and can be useful fortherapeutic applications

Parkia pendula seed lectin showed a potential healingeffect on cutaneous wounds in normal and immunocom-promised mice [131] The lectin was daily topically admin-istered in wounds produced in the dorsal region of miceHistopathological analysis revealed edema and hyperemiaduring inflammatory period no bacterium proliferationand complete wound closure were observed in normal andimmunocompromised groups treated with this lectin

Previous studies with plant lectins demonstrated theirpotential to stimulate the production of metalloproteinase-9 (MMP-9) that participates in different steps of woundhealing as chemoattractive factors for inflammatory cellsinductors of cytokines release and synthesis of collagen [132]Healing impaired is a relevant therapeutic problem in tissuerepair mainly for patients with diabetes and other diseaseswhich suffer from chronic wounds and require more carefor cicatrization In this context some lectins are prohealingnatural sourcemolecules very efficient for induction of fasterreepithelialization and cicatrization

5 Lectins for Drug Delivery

The therapies using chemical agents have some barriersmainly regarding the need of increasing dosages and action ofmetabolism which reduce the effectiveness of treatment Sys-tems for delivering drugs to a specific target may constituteinteresting and effective strategies to troubleshoot these prob-lems and minimize negative side effects [133] The controlleddeliverance techniques such as liposomes nanosuspensionsand bioadhesive systems provide an adequate release rateand duration producing the desired effect however theyhave a main disadvantage of nonspecificity to substrate [134]On the other hand the lectin-mediated bioadhesion con-stitutes specific establishing interactions with receptor-likestructures in cell membrane binding directly to target cells[135]


(a) (b)

(c) (d)

Figure 2 Histologic micrographs of wounds treated with Cramoll 14 and Con A in the 12th day in female albino Swiss mice A total woundclosure reepithelialization and deposition of collagen fibers are observed in Cramoll 14 treated group with 5120583g100 120583l (a) Cramoll 14treated group with 10 120583g100 120583l (b) and Con A (10 120583g100 120583l) treated group (c)The formation of well-developed cutaneous annexes is presentin Cramoll 14 (10120583g100 120583l) treated group (b) Incomplete reepithelialization without wound closure observed for control negative groupadministered with 150mM NaCl (d)

Since a set of cell surface proteins and lipids are glyco-sylated they can operate as lectin binding sites Differentcell types generally express glycoconjugates that differ in theglycosylation patterns as with tumor cells compared withtheir normal counterparts (Figure 3) In this sense lectins caninteract differently with distinct cells and may act as carriersof drugs specifically to desired cells and tissues [136] Tobe a potential tool for using in drug delivery lectins shouldbe of avid binding low toxicity and site-specific moleculesFigure 4 outlines the mechanism of bioadhesion by lectins

Lectins may interact on cell surface or be internalizedvia endocytosis mediated by receptors These molecules notonly allow a target specific attachment but also can promotea drug uptake actively mediated by the cell [137] Leonget al [138] reported that the oral administration of insulinentrapped into surface-lectin-functionalized microparticlesextended duration of the hypoglycemic effect up to 12ndash24 h in diabetic rats regarding the free insulin Neutschet al [139] showed that the covalent surface modificationof microparticles containing a gemcitabine derivative with

wheat germ agglutinin (WGA) resulted in enhancing ofbinding duration on urothelial cells bound microparticleswere able to withstand the extensive washout and improvedantiproliferative activity [139]

WGA covalently coupled with nanoparticles for carryingthymopentin [140] After conjugated with nanoparticles thelectin retained its specific carbohydrate-binding activity Inaddition the increase in WGA content on nanoparticlesenhanced oral uptake of thymopentin by improving absorp-tion of nanoparticles and protecting thymopentin againstdegradation Nanoparticles coupled with WGA allowedinvestigation for targeted delivery of 120573-galactosidase to theintestinal mucosa in Wistar rats Fluorometric methodsshowed that nanoparticles adhered to intestinal mucosa forprolonged period (67 h) corresponding to 69-fold higherthan nanoparticles without lectin Then authors stated thatWGA-nanoparticles are promising candidates for efficientmucosal drug delivery to treat lactose intolerance [141]

Liposomes modified with Con A had its degree ofmembrane adhesion significantly increased in comparison


ICM

ECM

Normal mucin

Lectin

(a)

Lectin

ICM

ECM

Tumor associatedmucin

(b)

Figure 3 Differential interaction of lectins with cells expressing diverse glycosylation patternMucins constitute a glycosylated protein familywith high molecular weight expressed by epithelial tissues In normal cells (a) the mucin is extensively glycosylated and more than 50 ofits molecular mass corresponds to oligosaccharide chains which may be difficult or impair the interaction of lectins and the carbohydrateresidues frommucin On the other hand in its tumor counterparts (b) the mucin generally has fewer oligosaccharide side chains which mayfacilitate the binding between lectins and glycosylated sites ECM = extracellular medium ICM = intracellular medium

ECM

ICM

Lectin

microparticleSurface-lectin-functionalized

Drug

Figure 4 Mechanism of lectin bioadhesion Glycoconjugates on cell surface (glycoproteins or glycolipids) can operate as lectin binding sitesECM = extracellular medium ICM = intracellular medium

with liposome without lectin [133] This adhesion followedby fusion of vesicles was also higher for Con A conjugatedliposomes than for unmodified liposomes Additionally ConA conjugated microspheres showed high attachment rate(837) in comparison with nonconjugated microspheres(167) and was able to control the release of the drugamoxicillin trihydrate in simulated gastrointestinal fluids[142]

Floating-mucoadhesive microparticles containing ethyl-cellulose and chitosan were loaded with clarithromycinand conjugated with Con A to form a lectin-drug carriercomplex against Helicobacter pylori The conjugation did notinterfere with the buoyancy and release of clarithromycinfrom microspheres using a mucus diffusion model About53 and 40 of drug were released from unconjugated andconjugated microspheres respectively within 12 h Lectinconjugation improved mucoadhesion and interaction with

porcine gastric mucin regarding unconjugated microspheres[143] Lectins from Pisum sativum seeds were encapsulatedin alginate microbeads for oral drug delivery against hepato-cellular carcinoma results showed that the release of lectinsfrom microbeads depended on a variety of factors includingmicrobead forming carriers and the amount of encapsulatedlectins [144]

Acosta et al [145] investigated the ricin B-chain (RTB)plant lectin which corresponds to the nontoxic carbohy-drate-binding B subunit of ricin AB toxin from Ricinuscommunis as a promising carrier for human lysosomalenzymes Authors genetically fused RTB with human 120572-L-iduronidase (IDUA) a lysosomal enzyme that degradesglycosaminoglycans The product of this fusion RTB IDUAretained both lectin selectivity and enzyme activity andtreated human fibroblasts from normal and iduronidase-deficient individualsThe results showed that RTB IDUAwas


Normal tissue

conjugated lectin

Hydrogen peroxide

Oxidated DAB

Peroxidase-

Peroxidase

Benign tumor tissue Malign tumor tissue

Normal tissue Benign tumor tissue Malign tumor tissue


DAB

Figure 5 Schematic representation of lectin histochemistry using peroxidase-conjugated lectins In this hypothetical case the lectin bindsglycan moieties more expressed on normal tissues which suffer a modification in their structure (eg sialylation or fucosylation) in benignand malign tumors tissues Thus the lectin binding increased in transformed tissues The DAB reagent in the presence of peroxidase andhydrogen peroxide was converted to DAB oxidized that precipitates as a brown product and allows visualization of lectin binding

efficiently endocytosed into human fibroblasts and able tocorrect the disease phenotype of mucopolysaccharidosis infibroblasts under in vitro conditions

Liposomes covered with Bauhinia purpurea agglutininwere evaluated as a drug delivery system to treat humanprostate cancerThe liposomes containing the lectinwere ableto bind DU145-cells in mice and suppress the growth of thecells [146]

6 Lectins as Histochemical Markers

The glycan moieties covering cell surfaces are involved inmany physiological and pathological processes related tocell Disturbances in cell environment related to diseasesfrequently trigger changes in glycans such as fucosylationsialylation abnormalities in glycan structure and uncom-mon glycans [147] Inflammation infections immunologicaldisorders and neoplasia have been associated with glycanchanges [148 149] In this context lectin abilities to bind car-bohydrates are useful to investigate changes in the expressionof glycans on cells in tissue surfaces Histochemical analysisusing conjugated lectins as potential markers for alteredglycans may show differential binding patterns to normaland transformed tissues [150] Generally lectin histochem-istry uses peroxidase-conjugated lectin followed by additionof diaminobenzidine (DAB) and hydrogen peroxidase for

visualization of binding as a hypothetical example in Fig-ure 5 This technique has been an approach for researchdiagnosis and prognosis of human diseases signalized byaltered cells in tissues such as cancer

Cramoll isoforms demonstrated specific binding patternsto normal and transformed human tissues Normal andtransformed (infiltrating duct carcinoma and fibroadenoma)mammary tissue sections were incubated with Cramoll 1and Con A conjugated to peroxidase the lectin bindingpatterns were visualized after interaction with DAB andhydrogen peroxidase Cramoll 1 marked neoplastic tissuesmore intensely than normal tissues similarly to Con A [151]Cramoll 14 and Cramoll 3 both conjugated to peroxidasewere evaluated as histochemical markers of normal hyper-plastic and carcinoma tissue samples from human prostatestaining patterns were compared with Con A and peanutagglutinin (PNA) results [46] Differential binding patternswere observed among normal hyperplastic and carcinomatissues Cramoll 14 and Con A showed more intense bindingin hyperplastic than normal samples and a distinct bindingpattern in carcinoma tissues reducing the staining with thegravity of tumor Cramoll 3 and PNA showed an increase ofstaining degree from normal to carcinoma tissues Cramoll1 Cramoll 14 and Cramoll 3 are potential histochemicalmarkers for normal and transformed mammary and prostatetissues


Helix pomatia agglutinin (HPA) histochemical analysisdetected cancer and metastatic cells in tissues Oligosaccha-rides on aggressive humanbreast cancerweremarked byHPAhistochemistry [152] After the histochemical lectin stain-ing oligosaccharides were released from lectin in order toinvestigate some correlation between HPA binding oligosac-charides and breast cancer A high level of monosialylatedoligosaccharide HPA binding expressed in breast cancerspecimens was observed showing a positive correlationbetween HPA binding and aggressiveness of breast cancer Arelation between HPA binding and metastasis was reportedin histochemical analysis of cutaneous malignant melanoma[153] The lectin stained tissue sections detected primarycutaneous malignant melanoma and a positive correlationbetween HPA binding and metastasis Apparently HPArecognized N-acetylgalactosamine or N-acetylglucosamineresidues on the cells and these carbohydrates have somerelation with metastasis formation in malignant melanomabeing useful as histochemical marker

In order to characterize glycosylation changes relatedto metastasis of breast and colon cancer cells a histo-chemical analysis with HPA and selectins was performed[154] The glycoprofiling binding of human breast and coloncancer cells metastasizing or nonmetastasizing was ana-lyzed by histochemistry using lectins among these HPA E-selectin and P-selectin HPA boundmetastasizing breast andcolon cancer cells while it did not bind nonmetastasizingcells An increase of selectin ligands on metastatic coloncancer cells was observed through E-selectin binding P-selectin binding was more intense in metastasizing breastcancer than nonmetastasizing ones Thus the lectin bind-ing properties are also useful to detect metastatic cancercells

Parkia pendula lectin (PpeL) conjugated to horseradishperoxidasewas evaluated as histochemicalmarker for charac-terization of meningothelial tumor tissue [155] PpeL showeddifferential staining pattern that allowed identifying themeningothelial subtype In addition a preferential PpeLbinding to cytoplasmatic glycans was observed These resultssuggest the potential of PpeL as histochemical marker usefulfor meningothelial tumor characterization and diagnosis

Ulex europeus agglutinin I (UEA-I) was indicated ascandidate to prognostic marker in ovarian cancer tissues[156] UEA-I showed a differential staining pattern related totumor stage Tumors with high malignancy stained by UEA-I since this lectin is fucose-specific it was suggested thatfucose residues increase with the degree of ovarian cancerAnother study analyzed the expression of tumor-associatedcarbohydrate antigen to in situ breast ductal carcinomausing lectin histochemistry to detect carbohydrates [157]The plant lectins Griffonia simplicifolia lectin-I (GS-I) andVicia villosa agglutinin (VVA) were used for breast cancertissue staining and results correlated to prognostic factorssuch as tumor size and grade as well as expression of othermarkers For both lectins more intense staining in specimenswith nuclear grades II and III than nuclear grade I wasobserved indicating a positive relation between expressionof carbohydrate antigen GS-I and VVA-binding and moreaggressive ductal carcinoma in situ

The potential of recombinant and native frutalin 120572-D-galactose-binding plant lectin from Artocarpus incisa seedsto marker human prostate tumor was evaluated [158]Prostate carcinoma and benign prostate hyperplasia tissueswere analyzed using the lectins conjugated with anti-frutalinpolyclonal antibody to react with a complex biotinylated anti-rabbit IgG and streptavidin-conjugated peroxidase followedby the addition of DAB for visualization of lectin stainingNative frutalin showed a preferential binding for carci-noma cells compared with hyperplasic cells recombinantfrutalinmarked only carcinoma cells showing heterogeneousbinding patterns Both lectins are useful for histochemicaldetection of prostate tumor

A study with human gastric cancer demonstrated asso-ciation between lectin binding and metastasis formation bylectin histochemistry [159] Maackia amurensis leukoagglu-tinin (MAL) histochemical staining was performed in orderto analyze the level expression of 120572 2 3-linked sialic acidresidues in gastric cancer samples and their association withmetastatic potential of one cell line High levels of 120572 23-linked sialic acid residues on gastric cancer cells wereevidenced by MAL as well as relation with potential ofinvasion and metastasis MAL is an efficient histochemicalmarker to human gastric cancer metastasis

Con A and UEA-I were used for histochemical analysisof parotid gland mucoepidermoid carcinoma (MEC) [160]MEC tissues of the parotid gland previously classified aslow intermediate and high grade were incubated withCon A and UEA-I conjugated with horseradish peroxidaseDifferential binding patterns for Con A and UEA-I stainingwere visualized Con A binding was observed in all grades ofMEC tissues but ductal cells of high and intermediate gradeswere less stained UEA-I bound intensively MEC tissues inlow grade moderately the cells in intermediate grade andweakly MEC cells in high grade

Lectin histochemistry has also detected fungal speciesinfecting human tissues binding carbohydrates of their cellwall surface Con A UEA-I WGA and PNA conjugatedwith horseradish peroxidase recognized the presence ofglucosemannose D-galactose L-fucose and N-acetyl D-glucosamine on the cell wall surfaces of Aspergillus speciesin human brain and lung specimens following the visu-alization with DAB and hydrogen peroxide Specimen tis-sues were obtained in patient autopsy diagnosed post-mortemwith invasive aspergillosisThe expression ofmethyl-120572-D-mannoside and N-acetyl D-glucosamine detected inAspergillus species by Con A and WGA staining showed thepresence of fungal structures in infected specimens of brainand lung tissues [161]

Generally lectin histochemistry uses enzyme-lectin con-jugated in order to reveal the lectin binding Glycoconjugatespresent in normal and transformed tissues have also beencharacterized by quantum dot-lectin histochemistry [162]Con A and UEA-I were conjugated with quantum dots tobind glycoconjugates on breast tissues in accordance withspecificities (120572-D-mannose and L-fucose residues respec-tively) The results revealed a differential expression anddistribution of sugar residues in normal and transformedbreast tissues showing distinct binding patterns


Lectin histochemistry is an attractive approach to marktransformed tissues and pathological events such as metas-tasis and shows differential lectin binding patterns that mayallow distinguishing between normal benign and maligntumor in various grades Lectins employed to investigate theglycan profile in transformed tissues constitute useful toolsfor diagnosis and prognosis of cancer

7 Lectin-Based Biosensors forDisease Detection

Many known biomarkers established to specific physio- andpathological processes are glycoprotein and glycan detectablein biological fluids and cell surface [163] Lectin assaysdeveloped for glycan analysis attached to circulating glyco-proteins or cell surfaces allowing the detection of diseasesand pathogens Lectin-based biosensors have been developedto detect and quantify glycans [164] These systems are basedon the conversion of lectin-carbohydrate interactions into ameasurable signal on a surface allowing the measurement ofbiomarkers

When compared to other lectin techniques such asenzyme-linked lectin assay and lectin microarrays whichuse labeled systems that generate color or fluorescencebiosensors can operate in a label-freemode reducing the stepsand consumption of reagents In accordance with type ofsignal transduction biosensingmethods can be electrochem-ical optical mass and thermal however electrochemicalbiosensors are more attractive since they are rapid practi-cal low cost and user-friendly assays available in distinctdesigns and analytical performance [164 165] Electrochem-ical biosensors have been constructed using electrodes assensing surfaces commonly modified with polymers andnanomaterials (carbon nanotubes gold magnetic nanoparti-cles etc) to improve the analytical performance and immo-bilization of biorecognition elements such as lectins [164]Techniques such as electrochemical impedance spectroscopy(EIS) and voltammetry are used to measure alterations onthe electrode surface and detect interaction ligand-analyte(Figure 6) EIS measurements are based on the detection ofchanges in charge transfer resistance on the sensor surfaceafter the interactions Voltammetric techniques such as cyclicvoltammetry (CV) differential pulse voltammetry (DPV)and square wave voltammetry (SWV) are based on detec-tion of changes in the current signals generated under theapplication of a potential on electrode in the presence of aredox probe [166] Electrochemical lectin-based biosensorsare more attractive as analytical tools of glycans and theirapplication in finding pathogens and diagnosis of diseasesreported through detection of biomarkers

The specific binding affinity of Con A for glucoseman-nose was explored in the development of biosensors fordistinct applications An electrochemical biosensor basedon Con A was developed for nonenzymatic recognition ofglucose [167] Con A immobilized onto thionine modifiedelectrodes established a sensing surface for specific recog-nition of glucose Con A biosensor detected glucose in lowconcentrations in a linear range from 10times 10minus6 to 10times 10minus4Machieved a good limit from detection of 75 times 10minus7M The

biosensor successfully determined glucose in serum samplesbeing a potential tool for blood glucose analysis monitored indiabetic individuals

An electrochemical biosensor based on Con A and goldnanoparticles-modified electrode was efficient to recognizeserum glycoproteins from patients infected by dengue virus[168] Another lectin biosensor based on Con A and lipidmembranes was constructed for electrochemical detection ofabnormal serum glycoproteins from patients contaminatedwith dengue serotypes I II and III (DSI DSII and DSIII)[169] EIS and CV revealed the interactions between ConA and glycoproteins from serum samples showing morequantitative response to glycoproteins from DSIII Con Arecognizes serum glycoproteins related to dengue infectionbeing useful for determination of dengue serotypes Anotherelectrochemical biosensor using Con A showed potential forrapid sensitive and selective detection of norovirus (NoV)[170]The biosensor was composed by a nanostructured goldelectrode with Con A immobilized in order to recognizeNoV The results showed a linear relation between currentsignals and concentration of NoV in the range of 102 and106 copiesmL a great detection limit of 35 copiesmL anda selectivity of 98 for NoV being an attractive approachfor sensitive and selective quantification of NoV in biologicalsamples

Sialylation is a common feature observed in glycansand glycoproteins in the occurrence of diseases electro-chemical lectin-based biosensors have been elaborated fordetermination of sialylated glycoproteins in solutions andbiological samples An ultrasensitive label-free biosensorusing the sialic acid-specific lectin Sambucus nigra agglutinintype I (SNA-I) immobilized on a self-assembled monolayer(SAM)was developed to quantify the sialylated glycoproteinsfetuin and asialofetuin [171] EIS measurements revealed thatSNA biosensor detected both glycoproteins in femtomolarlevel showing a promisor application for diagnosis of dis-eases associated with aberrant sialylation Another SNA-Ilectin biosensor using gold nanoparticles detected sialic acidresidues in fetuin and asialofetuin down to attomolar levelbesides identifying changes in the sialic acid amount [172]

Biosensors in a larger approach were constructed basedonConA SNA-I andRicinus communis agglutinin (RCA) onSAM-modified gold electrode in order tomeasure serum gly-coproteins in real samples [173] Glycoproteins were detectedin femtomolar level by all three lectin biosensors Later theywere incubated with human serum samples from healthyindividuals and people diagnosed with rheumatoid arthritis(RA) for glycoprofiling of glycan patterns Con A and RCAbiosensors signals for serum from healthy individuals wereweaker than signal for serum from RA patients suggesting alower exposition of mannose and galactose residues in serumglycans from healthy individuals SNA biosensor showedhigher signals for serum healthy individuals when comparedto serum from RA patients showing that the expression ofsialic acid in serum from RA patients is reduced it is pos-sible to distinguish these samples due to lectin specificitiesAnother SNA-I biosensor was developed for discriminationof cancer-associated sialyl-Tn (STn) antigen in real samples[174] SNA-I was immobilized onto screen-printed gold


ElectrodeElectrode

Lectin Glycoprotein

Glycan Cell

E (V)

I(휇

A)

EIS DPV

I(휇

A)

E (V)EIS DPV

A

B

A

B

A㰀

B㰀

(a) (b)

[Fe(CN)6]3minus4minus


Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Figure 6 Schematic representation of lectin-modified electrode surface before (a) and after binding (b) for measurements of lectin-glycaninteractions In the electrochemical system measurements are performed in a solution containing a redox probe (eg [Fe(CN)6]

3minus4minus)reduction or oxidation states generate electrochemical signals (charge transfer resistance for electrochemical impedance spectroscopy EISand current for differential pulse voltammetry DPV) to monitor electrode surface interactions Before binding (a) charge transfer resistanceor current signals are obtained on lectin-modified electrode surface After binding (b) the presence of cells or glycoproteins on electrodesurface generates a higher blockage for charge transfer and current signals It is measured as an increase in the charge transfer resistance(represented by semicircle A1015840) for EIS response and a reduction in the current amplitude for DPV response

electrodes and their surfaces were incubated with serumsamples fromhealthy individuals and patientswithmalignanttumors to analyze STn-expression in serum glycoproteinsEIS results revealed a differential interaction of SNA-I withSTn antigens in serum glycoproteins distinguishing betweenhealthy and cancer samples

Evaluation of mannose and sialic acid expression onnormal and cancer cells from human lung liver and prostatewas performed by an electrochemical lectin-based biosensorbased on Con A and SNA [175] Con A and SNA lectinswere used as biorecognition element for mannose and sialicacid respectively The proposed biosensor could successfullydetect the expression levels of specific sugars Sialic acid wasmore evident in cancer cells and mannose showed a highexpression in both normal and cancer cells The biosensorcould quantify cancer cells and measure the amount ofsialic acid expressed on single cell surface being a promiseapproach for profiling glycan expression on cell surfacesproviding an early diagnosis and treatment

Cramoll lectin biosensors have been reported for reve-lation of glycoproteins in solutions and serum samples byelectrochemical finding A biosensor was developed usinggold electrode modified with polyvinyl formal chloroformFe3O4 nanoparticles and Cramoll for exposure of fetuin insolutions and glycoproteins from serum patients contami-nated with DSI DSII and DSIII [176] EIS and voltammetricmeasurements showed the interaction of Cramoll with fetuinand serum glycoproteins of DSI DSII andDSIII and a higherresponse to glycoproteins of DSII Another Cramoll biosen-sor elaborated with gold nanoparticles polyaniline andCramoll was used to identify abnormal glycoproteins of DSIDSII andDSIII dengue fever and dengue hemorrhagic feverpresent in serum samples [177] EIS andCV characterizationsrevealed distinct changes in the charge transfer resistanceand current signals after interactions with the serum samplesbeing able to recognize serum glycoproteins from dengueserotypes A greater Cramoll binding was observed to DSIIIglycoproteins A label-free Cramoll nanosensor based on


assembled carboxylated carbon nanotubes and poly-L-lysinefilm showed differential serum glycoproteins from prostatecancer and benign prostatic hyperplasia [9] DPV responsesof nanosensor revealed that Cramoll was able to distinguishbetween benign and malign prostate tumor in addition toshowing a significant statistical correlation with the degreeof staging prostate cancer Another Cramoll biosensor con-tained self-assembled Cramoll lectin on the hybrid cysteine-gold nanoparticles-modified gold electrode and was used asa recognition interface for bacterial lipopolysaccharide (LPS)[10] CV and EIS results expressed the selective interactionsof Cramoll biosensor with LPS from Escherichia coli Serratiamarcescens Salmonella enterica and Klebsiella pneumoniaeThus Cramoll has been able to recognize bacterial LPSand serum glycoproteins becoming a potential approach fordiagnosis of diseases

The ability of lectins to recognize glycans in additionto the attractive analytical performance of electrochemicalbiosensors has been successfully applied for detection ofvirus and bacteria as well as glycoprofiling of serum glyco-proteins and cell surfaces Early discovered infections anddiseases can help in the diagnosis and appropriate treatment

8 Lectins as Anticancer Agents

Lectins from several origins exert cytotoxic effects suchas inhibition of proliferation and activation of cell deathpathways on different types of cancer cells In additionmany anticancer lectins usually possess low cytotoxicityto nontransformed cells This fact is probably associatedwith the distinct expression of glycans on surface of cancerand normal cells allowing lectins specifically to recognizemalignant cells [11 12]

The ability of lectins to inhibit the growth of cancer cells invitro is well documented in the literature and some examplesare listed in Table 1 [13ndash21 23ndash25 27ndash29 89 111 178ndash181] Inaddition to reduce cell proliferation lectinsmay interact withreceptors and other molecules present in cell surface andorcytosol activating cell death pathwaysMCF-7 (human breastcancer) and HCT-15 (human colorectal adenocarcinoma)cells treated with a lectin isolated from Morus alba leafshowedmorphological changes and DNA fragmentation thatare characteristic of death by apoptosis which was confirmedby the authors using staining with annexin V and acridineorangeethidium bromide in addition an increased activityof caspase 3 was detected [182] On the other hand theBauhinia forficata seed lectin induced necrosis and sec-ondary necrosis in MCF-7 cells with caspase 9 inhibition[21]

A mannose-binding lectin from Clematis montanainduced apoptosis in L929 cells (murine fibro sarcoma)with activation of caspases Authors proposed that thereis a correlation between carbohydrate-binding ability andanticancer effect of this lectin since the cytotoxic activitydecreased with the assay performed in presence of mannose[23] In the same sense Carvalho et al [20] attributed death ofNB4 (leukemia) cells promoted by Artocarpus heterophylluslectin to the recognition of a trimannosyl core of N-glycans

containing a 12057316-N-acetylglucosamine branch linked to 120572-16-mannose

Mechanisms of apoptosis or necrosis induction by lectinshave been studied The treatment of MCF-7 cells with lectinfrom Abelmoschus esculentus led to increasing in expressionof proapoptotic genes (caspase 3 caspase 9 and p21) as wellas increasedBaxBcl-2 ratio being Bax a proapoptotic proteinwith activity inhibited by Bcl-2 [19] Wu et al [181] reportedthatPolygonatumodoratum rhizome lectin induced apoptosisand autophagy in A549 cells (human adenocarcinoma fromalveolar basal epithelial cells) and demonstrated that thisactivity involves the regulation of microRNAs levels Authorsdescribed a downregulation of the microRNA-1290 whichleads to amplification of apoptosis and downregulation ofWnt pathway in addition the glycogen synthase kinase-3120573was reported as a direct target of thismicroRNAOn the otherhand authors mentioned upregulation of microRNA-15a-3pwhich mediates ROS-p53 44 pathway linked to apoptosis andautophagy Bothrops leucurus venom lectin triggered necrosisin B16-F10 (murine melanoma) cells with increase in cytoso-lic calcium concentration and mitochondrial superoxidegeneration this lectin activated the opening ofmitochondrialpermeability transition pore [16] Yang et al [183] showed thatdimerization and formation of a hydrophobic pocket in thestructure of an Agrocybe aegerita lectin are essential for itsapoptosis-inducing activity

Lectins may also affect the adhesion ability of cancercells Lebecin (a C-type lectin-like protein fromMacroviperalebetina venom) inhibited the integrin-mediated attachmentof MDA-MB-231 (human breast cancer) cells to fibronectinand fibrinogen [17] Bauhinia forficata seed lectin inhib-ited adhesion of MCF-7 cells to laminin collagen I andfibronectin by decreasing expression of12057211205726 and1205731 integrinsubunits [21]

As mentioned above lectins can reach the cytosol andpromote several alterations in cell physiology A remarkableexample is the lectin from Northeast China black beanswhich was reported to bind HCT116 (colorectal carcinoma)cell membrane and was found in the Golgi apparatusand lysosomes within 3 h after treatment Authors alsodescribed that this lectin caused aggregation of Golgi com-plex protein accumulation in the endoplasmic reticulummitochondrial malformation and membrane depolarization[29]

The several reports on the potential of lectins for cancertreatment stimulated studies at in vivo conditions usingdifferent models Crataeva tapia bark lectin showed anti-tumor activity on sarcoma 180 (ascitic tumor) model andits safety for use in future clinical studies was indicatedby the low toxicity (LD50 of 2500mgkg) to mice [184]Lectins isolated from fruiting bodies of Russula lepida andPleurotus citrinopileatus also showed antitumor activity inmice reducing in 80 and 673 respectively the growth ofsarcoma 180 tumor [185 186]

Cratylia mollis seed lectin encapsulated into liposomeswas evaluated for in vivo antitumor activity against sarcoma180 Shrinkage and 71 inhibition of tumor growth weredetected in comparison with untreated group encapsulationprevented lectin-damaging effects (fibrosis necrosis and


Table 1 Sources of lectins with in vitro inhibitory effect on growth of different cancer cells

Source Affected cells ReferenceFungi

Agrocybe aegerita

HeLa (derived from cervical cancer cells)HL-60 (promyelocytic leukemia) SW480

(lymph node metastasis) SGC-7901BGC-823 and MGC80-3 (gastric cancer)

[9]

AnimalsAristichthys nobilis gills HeLa [10]

Bothrops leucurus venom

B16-F10 (murine skin melanoma) HEp-2(carcinoma) K562 (chronic myelogenous

leukemia) NCI-H292 (lungmucoepidermoid carcinoma)

[11 12]

Macrovipera lebetina venom MDA-MB-231 (human breast cancer) [13]Plants

Abelmoschus esculentus seeds MCF-7 (breast cancer) [14]Amaranthus mantegazzianus seeds URM-106 (rat osteocarcinoma) [15]Artocarpus heterophyllus seeds NB4 (leukemia) [16]Bauhinia forficata seeds MCF-7 [17]

Clematis montana stem L929 (murine fibrosarcoma) HepG2(hepatocellular carcinoma) HeLa MCF-7 [18]

Dioscorea opposita tubers CNE-2 (nasopharyngeal carcinoma)MCF-7 HepG2 [19]

Glycine max seeds U373MG (glioblastoma astrocytoma)HeLa HEp-2 HepG2 MDA-MB-231 [20]

Lotus corniculatus THP-1 (leukemia) HOP62 (lungadenocarcinoma) [21]

Microgramma vacciniifolia rhizome NCI-H292 [22]Momordica charantia seeds EAC (Ehrlich ascites carcinoma) [23]

Morus alba leaves HCT-15 (colorectal adenocarcinoma)MCF-7 [9]

Northeast China black beans HCT116 (colorectal carcinoma) [24]Phaseolus vulgaris cv extra long autumnpurple bean seeds

HNE-2 CNE-1 CNE-2 (nasopharyngealcarcinoma) MCF-7 HepG2 [25]

P vulgaris Chinese pinto bean seeds HONE-1 (nasopharyngeal carcinoma) [26]P vulgaris cv blue tiger king seeds HepG2 [27]Pisum sativum seeds EAC cells [28]

Polygonatum odoratum A549 (alveolar basal epithelialadenocarcinoma) [29]

lymphocyte infiltration) that were observed in liver andkidney of animals treated with free lectin solution [187]

Pisum sativum and Momordica charantia seed lectinsshowed in vitro and in vivo inhibitory effects on Ehrlichcarcinoma (ascitic tumor) in mice The growth of tumorinhibited in 63 and 75 with P sativum and M charantialectins respectively both administered intraperitoneally at28mgkgday for five consecutive days The P sativum lectincaused apoptosis involving activation of caspases while theM charantia lectin did not induce this cell death mechanismThe proapoptotic gene Bax was expressed intensively in cellstreated with P sativum lectin [28 180] The seed lectin fromGlycine max caused 8295 inhibition of Daltonrsquos lymphomain mice that received it through intraperitoneal injectioninduction of autophagy and apoptosis with activation of ROSproduction was detected [25]

Finally the anticancer potential of lectins also includesantimetastatic properties Leaf lectin from Viscum albumcoloratum showed a preventive effect against lung metastasiscaused by B16-BL6 and 26-M31 cells in mice that received20ndash50 ng of lectin through intravenous administration twodays before inoculation of cancer cells This lectin alsoinhibited liver and spleen metastasis of L5178Y-ML25 cellswhen administered one day after tumor inoculation [188]

9 Conclusions

Lectins from diverse sources with distinct carbohydraterecognition events have important roles for many biotech-nological applications and disease therapies In vitro and invivo uses showed that lectins have protective effects againstvirus and microorganisms they are potent modulators of


immune response mitosis proliferation healing drug deliv-ery therapies and cancer regression Altered glycans oncells or tissue surfaces and serum samples can be locatedusing lectin-based techniques such as histochemistry andbiosensors detecting diseases and infection agents Thusthis review gathers achievements attributed to lectins withfocus in biotechnologicalpharmacological and therapeuticapplications being a valuable resource formore studies aboutbiological effects pathways and biotechnological potentialof lectins Besides the effects described for the same ordifferent lectins on biological systems could unravel newinterpretations or insights to the field

Competing Interests

The authors have declared that no competing interests exist

Acknowledgments

TheConselhoNacional deDesenvolvimentoCientıfico e Tec-nologico (CNPq) is acknowledged for fellowships (LCBBCVLML PMGP and MTSC) and grants The authors are alsograteful to the Coordenacao de Aperfeicoamento de Pessoalde Nıvel Superior (CAPES) and the Fundacao de Amparo aCiencia e Tecnologia do Estado de Pernambuco (FACEPE)

References

[1] N Sharon and H Lis ldquoHistory of lectins from hemagglutininsto biological recognitionmoleculesrdquoGlycobiology vol 14 no 11pp 53Rndash62R 2004

[2] N Sharon ldquoLectins carbohydrate-specific reagents and biolog-ical recognitionmoleculesrdquoThe Journal of Biological Chemistryvol 282 no 5 pp 2753ndash2764 2007

[3] M Ambrosi N R Cameron and B G Davis ldquoLectins toolsfor the molecular understanding of the glycocoderdquo Organic ampBiomolecular Chemistry vol 3 no 9 pp 1593ndash1608 2005

[4] A M Wu E Lisowska M Duk and Z Yang ldquoLectins as toolsin glycoconjugate researchrdquo Glycoconjugate Journal vol 26 no8 pp 899ndash913 2009

[5] M A A Hassan R Rouf E Tiralongo T W May and J Tira-longo ldquoMushroom lectins specificity structure and bioactivityrelevant to human diseaserdquo International Journal of MolecularSciences vol 16 no 4 pp 7802ndash7838 2015

[6] A F S Santos T H Napoleao R F Bezerra et al ldquoStrategiesto obtain lectins from distinct sourcesrdquo inAdvances inMedicineandBiology L V Berhardt Ed vol 63 pp 33ndash60Nova ScienceNew York NY USA 2013

[7] S K Lam and T B Ng ldquoLectins production and practicalapplicationsrdquo Applied Microbiology and Biotechnology vol 89no 1 pp 45ndash55 2011

[8] L C N da Silva C M B Filho R A de Paula L C B BCoelho M V da Silva and M T D S Correia ldquoCratylia mollislectin a versatile tool for biomedical studiesrdquo Current BioactiveCompounds vol 10 no 1 pp 44ndash54 2014

[9] P M S Silva A L R Lima B V M Silva L C B BCoelho R F Dutra andM T S Correia ldquoCratylia mollis lectinnanoelectrode for differential diagnostic of prostate cancer andbenign prostatic hyperplasia based on label-free detectionrdquoBiosensors and Bioelectronics vol 85 pp 171ndash177 2016

[10] M D L Oliveira C A S Andrade M T S Correia L C BB Coelho P R Singh and X Zeng ldquoImpedimetric biosensorbased on self-assembled hybrid cystein-gold nanoparticles andCramoLL lectin for bacterial lipopolysaccharide recognitionrdquoJournal of Colloid and Interface Science vol 362 no 1 pp 194ndash201 2011

[11] M Przybyło D Hoja-Lukowicz A Litynska and P LaidlerldquoDifferent glycosylation of cadherins from human bladder non-malignant and cancer cell linesrdquo Cancer Cell International vol2 article 6 2002

[12] A Varki R Kannagi and B P Toole ldquoGlycosylation changes incancerrdquo in Essentials of Glycobiology A Varki R D CummingsJ D Esko et al Eds Cold Spring Harbor Laboratory PressCold Spring Harbor NY USA 2nd edition 2009

[13] C Zhao H Sun X Tong and Y Qi ldquoAn antitumour lectin fromthe edible mushroom Agrocybe aegeritardquo Biochemical Journalvol 374 no 2 pp 321ndash327 2003

[14] D Yao S Pan and M Zhou ldquoStructural characterizationand antitumor and mitogenic activity of a lectin from thegill of bighead carp (Aristichthys nobilis)rdquo Fish Physiology andBiochemistry vol 38 no 6 pp 1815ndash1824 2012

[15] E S Nunes M A A Souza A F M Vaz et al ldquoCytotoxic effectand apoptosis induction by Bothrops leucurus venom lectin ontumor cell linesrdquo Toxicon vol 59 no 7-8 pp 667ndash671 2012

[16] M A Aranda-Souza F A Rossato R A P Costa et al ldquoA lectinfrom Bothrops leucurus snake venom raises cytosolic calciumlevels and promotes B16-F10 melanoma necrotic cell death viamitochondrial permeability transitionrdquo Toxicon vol 82 pp 97ndash103 2014

[17] J Jebali E Fakhfekh M Morgen et al ldquoLebecin a new C-typelectin like protein fromMacrovipera lebetina venom with anti-tumor activity against the breast cancer cell line MDA-MB231rdquoToxicon vol 86 pp 16ndash27 2014

[18] A V Quiroga D A Barrio and M C Anon ldquoAmaranth lectinpresents potential antitumor propertiesrdquo LWTmdashFood Scienceand Technology vol 60 no 1 pp 478ndash485 2015

[19] L G Monte T Santi-Gadelha L B Reis et al ldquoLectin ofAbelmoschus esculentus (okra) promotes selective antitumoreffects in human breast cancer cellsrdquo Biotechnology Letters vol36 no 3 pp 461ndash469 2014

[20] F C Carvalho S G Soares M B Tamarozzi E M Rego andM-C Roque-Barreira ldquoThe recognition of N-glycans by thelectin ArtinMmediates cell death of a humanmyeloid leukemiacell linerdquo PLoS ONE vol 6 no 11 Article ID e27892 2011

[21] M C C Silva C A A De Paula J G Ferreira et alldquoBauhinia forficata lectin (BfL) induces cell death and inhibitsintegrin-mediated adhesion on MCF7 human breast cancercellsrdquo Biochimica et Biophysica Acta vol 1840 no 7 pp 2262ndash2271 2014

[22] M J Redondo and P Alvarez-Pellitero ldquoThe effect of lectinson the attachment and invasion of Enteromyxum scophthalmi(Myxozoa) in turbot (Psetta maxima L) intestinal epitheliumin vitrordquo Experimental Parasitology vol 126 no 4 pp 577ndash5812010

[23] H Peng H Lv YWang et al ldquoClematis montana lectin a novelmannose-binding lectin from traditional Chinese medicinewith antiviral and apoptosis-inducing activitiesrdquo Peptides vol30 no 10 pp 1805ndash1815 2009

[24] Y S Chan and T B Ng ldquoA lectin with highly potent inhibitoryactivity toward breast cancer cells from edible tubers ofDioscorea opposita cvNagaimordquoPLOSONE vol 8 no 1 ArticleID e54212 2013


[25] P K Panda S Mukhopadhyay B Behera et al ldquoAntitumoreffect of soybean lectin mediated through reactive oxygenspecies-dependent pathwayrdquo Life Sciences vol 111 no 1ndash2 pp27ndash35 2014

[26] R A Sa F S Gomes T H Napoleao et al ldquoAntibacterial andantifungal activities of Myracrodruon urundeuva heartwoodrdquoWood Science and Technology vol 43 no 1-2 pp 85ndash95 2009

[27] S Rafiq RMajeedAKQazi et al ldquoIsolation and antiprolifera-tive activity of Lotus corniculatus lectin towards human tumourcell linesrdquo Phytomedicine vol 21 no 1 pp 30ndash38 2013

[28] S R Kabir M M Nabi M Nurujjaman et al ldquoMomordicacharantia seed lectin toxicity bacterial agglutination and anti-tumor propertiesrdquo Applied Biochemistry and Biotechnology vol175 no 5 pp 2616ndash2628 2015

[29] X Dan T B Ng J H Wong Y S Chan R C F Cheung andW Y Chan ldquoA hemagglutinin isolated from Northeast Chinablack beans induced mitochondrial dysfunction and apoptosisin colorectal cancer cellsrdquo Biochimica et Biophysica Acta vol1863 no 9 pp 2201ndash2211 2016

[30] W Van Breedam S Pohlmann H W Favoreel R J de Grootand H J Nauwynck ldquoBitter-sweet symphony glycan-lectininteractions in virus biologyrdquo FEMS Microbiology Reviews vol38 no 4 pp 598ndash632 2014

[31] R S Singh A K Tiwary and J F Kennedy ldquoLectins sourcesactivities and applicationsrdquo Critical Reviews in Biotechnologyvol 19 no 2 pp 145ndash178 2008

[32] N Sharon ldquoBacterial lectins cell-cell recognition and infectiousdiseaserdquo FEBS Letters vol 217 no 2 pp 145ndash157 1987

[33] T K Lindhorst ldquoSmall molecule ligands for bacterial lectinsletters of an antiadhesive glycopolymer coderdquo in GlycopolymerCode Synthesis of Glycopolymers and Their Applications C RBecer and L Hartmann Eds pp 1ndash16 The Royal Society ofChemistry 2015

[34] T Sato and K Hori ldquoCloning expression and characterizationof a novel anti-HIV lectin from the cultured cyanobacteriumOscillatoria agardhiirdquo Fisheries Science vol 75 no 3 pp 743ndash753 2009

[35] B Hoorelbeke D Huskens G Ferir et al ldquoActinohivin abroadly neutralizing prokaryotic lectin inhibitsHIV-1 infectionby specifically targeting high-mannose-type glycans on thegp120 enveloperdquo Antimicrobial Agents and Chemotherapy vol54 no 8 pp 3287ndash3301 2010

[36] D Huskens G Ferir K Vermeire et al ldquoMicrovirin anovel 120572(12)-mannose-specific lectin isolated from Microcystisaeruginosa has anti-HIV-1 activity comparable with that ofcyanovirin-N but a much higher safety profilerdquo Journal ofBiological Chemistry vol 285 no 32 pp 24845ndash24854 2010

[37] A Varrot S M Basheer and A Imberty ldquoFungal lectinsstructure function and potential applicationsrdquoCurrent Opinionin Structural Biology vol 23 no 5 pp 678ndash685 2013

[38] R S Singh H P Kaur and J Singh ldquoPurification and charac-terization of a mucin specific mycelial lectin from Aspergillusgorakhpurensis application for mitogenic and antimicrobialactivityrdquo PLoS ONE vol 9 no 10 Article ID e109265 2014

[39] Y Watanabe T Naganuma T Ogawa and K MuramotoldquoLectins of marine origin and their clinical applicationsrdquoAntitumor Potential and other Emerging Medicinal Properties ofNatural Compounds pp 33ndash54 2013

[40] D C Kilpatrick ldquoAnimal lectins a historical introduction andoverviewrdquo Biochimica et Biophysica ActamdashGeneral Subjects vol1572 no 2-3 pp 187ndash197 2002

[41] Z Liu Q Zhang H Peng and W Zhang ldquoAnimal lectinspotential antitumor therapeutic targets in apoptosisrdquo AppliedBiochemistry and Biotechnology vol 168 no 3 pp 629ndash6372012

[42] O Akkouh T B Ng S S Singh et al ldquoLectins with anti-HIVactivity a reviewrdquoMolecules vol 20 no 1 pp 648ndash668 2015

[43] P L De Hoff L M Brill and A M Hirsch ldquoPlant lectins theties that bind in root symbiosis and plant defenserdquo MolecularGenetics and Genomics vol 282 no 1 pp 1ndash15 2009

[44] A U Hivrale and A G Ingale ldquoPlant as a plenteous reserve oflectinrdquo Plant Signaling and Behavior vol 8 no 12 Article IDe26595 2013

[45] J D SouzaM B R Silva A C C Argolo et al ldquoA newBauhiniamonandra galactose-specific lectin purified in milligram quan-tities from secondary roots with antifungal and termiticidalactivitiesrdquo International Biodeterioration and Biodegradationvol 65 no 5 pp 696ndash702 2011

[46] A L de Lima C C CavalcantiMC Silva et al ldquoHistochemicalevaluation of human prostatic tissues with Cratylia mollis seedlectinrdquo Journal of Biomedicine and Biotechnology vol 2010Article ID 179817 6 pages 2010

[47] A Vitlic J M Lord and A C Phillips ldquoStress ageing and theirinfluence on functional cellular and molecular aspects of theimmune systemrdquo Age (Dordrecht Netherlands) vol 36 2014

[48] S B Majee and G R Biswas ldquoExploring plant lectins indiagnosis prophylaxis and therapyrdquo Journal of Medicinal PlantsResearch vol 7 no 47 pp 3444ndash3451 2013

[49] O P Chilson andA E Kelly-Chilson ldquoMitogenic lectins bind tothe antigen receptor on human lymphocytesrdquo European Journalof Immunology vol 19 no 2 pp 389ndash396 1989

[50] M T Ashraf and R H Khan ldquoMitogenic lectinsrdquo MedicalScience Monitor vol 9 no 11 pp RA265ndashRA269 2003

[51] H X Wang W K Liu T B Ng V E C Ooi and S T ChangldquoThe immunomodulatory and antitumor activities of lectinsfrom the mushroom Tricholoma mongolicumrdquo Immunophar-macology vol 31 no 2-3 pp 205ndash211 1996

[52] Q-B She T-B Ng and W-K Liu ldquoA novel lectin withpotent immunomodulatory activity isolated from both fruitingbodies and culturedmycelia of the ediblemushroomVolvariellavolvaceardquo Biochemical and Biophysical Research Communica-tions vol 247 no 1 pp 106ndash111 1998

[53] P H K Ngai and T B Ng ldquoA mushroom (Ganoderma capense)lectin with spectacular thermostability potent mitogenic activ-ity on splenocytes and antiproliferative activity toward tumorcellsrdquo Biochemical and Biophysical Research Communicationsvol 314 no 4 pp 988ndash993 2004

[54] Y R Li Q H Liu H X Wang and T B Ng ldquoA novel lectinwith potent antitumor mitogenic and HIV-1 reverse transcrip-tase inhibitory activities from the edible mushroom Pleurotuscitrinopileatusrdquo Biochimica et Biophysica Acta (BBA)mdashGeneralSubjects vol 1780 no 1 pp 51ndash57 2008

[55] YDitamo L L Rupil V G Sendra G ANores G A Roth andF J Irazoqui ldquoIn vivo immunomodulatory effect of the lectinfrom edible mushroom Agaricus bisporusrdquo Food and Functionvol 7 no 1 pp 262ndash269 2016

[56] R S Singh R Bhari V Rana and A K Tiwary ldquoImmunomod-ulatory and therapeutic potential of a mycelial lectin fromaspergillus nidulansrdquo Applied Biochemistry and Biotechnologyvol 165 no 2 pp 624ndash638 2011

[57] K Hori H Matsuda K Miyazawa and K Ito ldquoA mitogenicagglutinin from the red alga Carpopeltis flabellatardquo Phytochem-istry vol 26 no 5 pp 1335ndash1338 1987


[58] R L C Rivanor H V Chaves D R Do Val et al ldquoAlectin from the green seaweed Caulerpa cupressoidesreducesmechanical hyper-nociception and inflammation in the rattemporomandibular joint during zymosan-induced arthritisrdquoInternational Immunopharmacology vol 21 no 1 pp 34ndash432014

[59] X Cao D Mao C Wang et al ldquoA d-galactose-binding lectinwith mitogenic activity fromMusca domestica pupaerdquo Zoologi-cal Science vol 26 no 4 pp 249ndash253 2009

[60] Y W Lam and T B Ng ldquoPurification and characterizationof a rhamnose-binding lectin with immunoenhancing activityfrom grass carp (Ctenopharyngodon idellus) ovariesrdquo ProteinExpression and Purification vol 26 no 3 pp 378ndash385 2002

[61] T B Ng YW Lam andN Y SWoo ldquoThe immunostimulatoryactivity and stability of grass carp (Ctenopharyngodon idellus)roe lectinrdquo Veterinary Immunology and Immunopathology vol94 no 3-4 pp 105ndash112 2003

[62] P H K Ngai and T B Ng ldquoA mannose-specific tetramericlectin with mitogenic and antibacterial activities from theovary of a teleost the cobia (Rachycentron canadum)rdquo AppliedMicrobiology andBiotechnology vol 74 no 2 pp 433ndash438 2007

[63] M C Coriolano C M L De Melo A J G Santos V RA Pereira and L C B B Coelho ldquoRachycentron canadum(cobia) lectin promoted mitogenic response in mice BALBcsplenocytesrdquo Scandinavian Journal of Immunology vol 76 no6 pp 567ndash572 2012

[64] M C Coriolano C D C da Silva C M L de Melo et alldquoImmunomodulatory response of mice splenocytes induced byRcaL a lectin isolated from cobia fish (Rachycentron canadum)serumrdquo Applied Biochemistry and Biotechnology vol 168 no 5pp 1335ndash1348 2012

[65] C D C Da Silva M C Coriolano M A Da Silva Lino etal ldquoPurification and characterization of a mannose recogni-tion lectin from Oreochromis niloticus (Tilapia Fish) cytokineproduction in mice splenocytesrdquo Applied Biochemistry andBiotechnology vol 166 no 2 pp 424ndash435 2012

[66] L G Baum M Pang N L Perillo et al ldquoHuman thymicepithelial cells express an endogenous lectin galectin-1 whichbinds to core 2 O-glycans on thymocytes and T lymphohlastoidcellsrdquo Journal of Experimental Medicine vol 181 no 3 pp 877ndash887 1995

[67] N L Perillo C H Uittenbogaart J T Nguyen and L GBaum ldquoGalectin-1 an endogenous lectin produced by thymicepithelial cells induces apoptosis of human thymocytesrdquo TheJournal of Experimental Medicine vol 185 no 10 pp 1851ndash18581997

[68] F Novelli A Allione V Wells G Forni and L MalluccildquoNegative cell cycle control of human T cells by 120573-galactosidebinding protein (120573GBP) induction of programmed cell deathin leukaemic cellsrdquo Journal of Cellular Physiology vol 178 no 1pp 102ndash108 1999

[69] G A Rabinovich N Rubinstein and M A Toscano ldquoRole ofgalectins in inflammatory and immunomodulatory processesrdquoBiochimica et Biophysica ActamdashGeneral Subjects vol 1572 no2-3 pp 274ndash284 2002

[70] R-Y Yang D K Hsu and F-T Liu ldquoExpression of galectin-3 modulates T-cell growth and apoptosisrdquo Proceedings of theNational Academy of Sciences of the United States of Americavol 93 no 13 pp 6737ndash6742 1996

[71] Y van Kooyk J M Ilarregui and S J van Vliet ldquoNovel insightsinto the immunomodulatory role of the dendritic cell and

macrophage-expressed C-type lectin MGLrdquo Immunobiologyvol 220 no 2 pp 185ndash192 2015

[72] E H Teixeira F V S Arruda K S do Nascimento et alldquoBiological applications of plants and algae lectins an overviewrdquoin Carbohydrates-Comprehensive Studies on Glycobiology andGlycotechnology C F Chang Ed InTech Rijeka Croatia 2012

[73] H-Y Lei and C-P Chang ldquoInduction of autophagy byconcanavalin A and its application in anti-tumor therapyrdquoAutophagy vol 3 no 4 pp 402ndash404 2007

[74] J Y Lee J Y Kim Y G Lee et al ldquoIn vitro immunoregulatoryeffects of Korean mistletoe lectin on functional activation ofmonocytic and macrophage-like cellsrdquo Biological and Pharma-ceutical Bulletin vol 30 no 11 pp 2043ndash2051 2007

[75] S Tripathi and T K Maiti ldquoImmunomodulatory role ofnative and heat denatured agglutinin from Abrus precatoriusrdquoInternational Journal of Biochemistry and Cell Biology vol 37no 2 pp 451ndash462 2005

[76] F de Oliveira Silva P das Neves Santos C M de Melo et alldquoImmunostimulatory activity of ConBr a focus on splenocyteproliferation and proliferative cytokine secretionrdquo Cell andTissue Research vol 346 pp 237ndash244 2011

[77] E V MMaciel V S Araujo-Filho M Nakazawa Y M GomesL C B B Coelho and M T S Correia ldquoMitogenic activity ofCratylia mollis lectin on human lymphocytesrdquo Biologicals vol32 no 1 pp 57ndash60 2004

[78] C M L de Melo H Melo M T S Correia L C B BCoelho M B da Silva and V R A Pereira ldquoMitogenicresponse and cytokine production induced byCramoll 14 lectinin splenocytes of inoculated micerdquo Scandinavian Journal ofImmunology vol 73 no 2 pp 112ndash121 2011

[79] C M L De Melo B A Paim K G Zecchin et al ldquoCramoll 14lectin increases ROS production calcium levels and cytokineexpression in treated spleen cells of ratsrdquoMolecular and CellularBiochemistry vol 342 no 1-2 pp 163ndash169 2010

[80] C M de Melo M C de Castro A P de Oliveira et alldquoImmunomodulatory response of Cramoll 14 lectin on experi-mental lymphocytesrdquo Phytotherapy Research vol 24 no 11 pp1631ndash1636 2010

[81] P S S D Oliveira M J B D M Rego R R Da Silva etal ldquoCratylia mollis 1 4 lectin a new biotechnological tool inIL-6 IL-17A IL-22 and IL-23 induction and generation ofimmunological memoryrdquo BioMed Research International vol2013 Article ID 263968 6 pages 2013

[82] L C N da Silva N M P Alves M C A B de Castroet al ldquoImmunomodulatory effects of pCramoll and rCramollon peritoneal exudate cells (PECs) infected and non-infectedwith Staphylococcus aureusrdquo International Journal of BiologicalMacromolecules vol 72 pp 848ndash854 2015

[83] P R Pereira E M Del Aguila M A Verıcimo R B Zingali VM F Paschoalin and J T Silva ldquoPurification and characteriza-tion of the lectin from taro (Colocasia esculenta) and its effecton mouse splenocyte proliferation in vitro and in vivordquo ProteinJournal vol 33 no 1 pp 92ndash99 2014

[84] A Butle S Talmale and M B Patil ldquoPotential in vivoimmunomodulatory effects of the most active lectin isolatedfrom seeds of Zizyphus oenopliardquo Journal of Clinical amp CellularImmunology vol 7 no 1 article 386 2016

[85] F Clement S N Pramod and Y P Venkatesh ldquoIdentity ofthe immunomodulatory proteins from garlic (Allium sativum)with the major garlic lectins or agglutininsrdquo InternationalImmunopharmacology vol 10 no 3 pp 316ndash324 2010


[86] V K Prasanna and Y P Venkatesh ldquoCharacterization of onionlectin (Allium cepa agglutinin) as an immunomodulatory pro-tein inducingTh1-type immune response in vitrordquo InternationalImmunopharmacology vol 26 no 2 pp 304ndash313 2015

[87] A C M B Sansone M Sansone C T S Dias and J R O doNascimento ldquoOral administration of banana lectin modulatescytokine profile and abundance of T-cell populations in micerdquoInternational Journal of Biological Macromolecules vol 89 pp19ndash24 2016

[88] X Y Ye T B Ng P W K Tsang and J Wang ldquoIsolation of ahomodimeric lectinwith antifungal and antiviral activities fromred kidney bean (Phaseolus vulgaris) seedsrdquo Journal of ProteinChemistry vol 20 no 5 pp 367ndash375 2001

[89] A S W Ang R C F Cheung X Dan Y S Chan W Pan andT B Ng ldquoPurification and characterization of a glucosamine-binding antifungal lectin from Phaseolus vulgaris cv ChinesePinto Beans with antiproliferative activity towards nasopharyn-geal carcinoma cellsrdquo Applied Biochemistry and Biotechnologyvol 172 no 2 pp 672ndash686 2014

[90] X-MHe N Ji X-C Xiang P Luo and J-K Bao ldquoPurificationcharacterization and molecular cloning of a novel antifungallectin from the roots of ophioglossum pedunculosumrdquo AppliedBiochemistry and Biotechnology vol 165 no 7-8 pp 1458ndash14722011

[91] L P De Albuquerque G M De Sa Santana T H NapoleaoL C B B Coelho M V Da Silva and P M G Paiva ldquoAnti-fungal activity of Microgramma vacciniifolia rhizome lectin ongenetically distinct Fusarium oxysporum f sp lycopersiciracesrdquoApplied Biochemistry andBiotechnology vol 172 no 2 pp 1098ndash1105 2014

[92] Q Yan Z Jiang S Yang W Deng and L Han ldquoA novelhomodimeric lectin from Astragalus mongholicus with antifun-gal activityrdquo Archives of Biochemistry and Biophysics vol 442no 1 pp 72ndash81 2005

[93] Q Yao C-FWu P Luo et al ldquoA new chitin-binding lectin fromrhizome of Setcreasea purpurea with antifungal antiviral andapoptosis-inducing activitiesrdquo Process Biochemistry vol 45 no9 pp 1477ndash1485 2010

[94] M B Trindade J L S Lopes A Soares-Costa et al ldquoStructuralcharacterization of novel chitin-binding lectins from the genusArtocarpus and their antifungal activityrdquo Biochimica et Biophys-ica ActamdashProteins and Proteomics vol 1764 no 1 pp 146ndash1522006

[95] P H K Ngai and T B Ng ldquoA lectin with antifungal and mito-genic activities from red cluster pepper (Capsicum frutescens)seedsrdquo Applied Microbiology and Biotechnology vol 74 no 2pp 366ndash371 2007

[96] J Wu J Wang S Wang and P Rao ldquoLunatin a novellectin with antifungal and antiproliferative bioactivities fromPhaseolus lunatus billbrdquo International Journal of BiologicalMacromolecules vol 89 pp 717ndash724 2016

[97] Q TianWWang CMiao et al ldquoPurification characterizationand molecular cloning of a novel mannose-binding lectin fromrhizomes ofOphiopogon japonicuswith antiviral and antifungalactivitiesrdquo Plant Science vol 175 no 6 pp 877ndash884 2008

[98] P Ghosh S Sen J Chakraborty and S Das ldquoMonitoring theefficacy of mutated Allium sativum leaf lectin in transgenic riceagainst Rhizoctonia solanirdquo BMC Biotechnology vol 16 no 1article 24 2016

[99] M Regente G B Taveira M Pinedo et al ldquoA sunflower lectinwith antifungal properties and putative medical mycology

applicationsrdquo Current Microbiology vol 69 no 1 pp 88ndash952014

[100] D d Ramos F S Gomes T H Napoleao P M Paiva M Dda Silva and L C Barroso Coelho ldquoAntimicrobial activity ofCladonia verticillaris lichen preparations on bacteria and fungiof medical importancerdquo Chinese Journal of Biology vol 2014Article ID 219392 7 pages 2014

[101] G B Klafke GM S GMoreira L GMonte et al ldquoAssessmentof plant lectin antifungal potential against yeasts of majorimportance in medical mycologyrdquoMycopathologia vol 175 no1-2 pp 147ndash151 2013

[102] A Q Pinheiro D F Melo L M MacEdo et al ldquoAntifungaland marker effects of Talisia esculenta lectin on Microsporumcanis in vitrordquo Journal of Applied Microbiology vol 107 no 6pp 2063ndash2069 2009

[103] I V Chikalovets O V Chernikov M V Pivkin et al ldquoAlectin with antifungal activity from the mussel Crenomytilusgrayanusrdquo Fish and Shellfish Immunology vol 42 no 2 pp 503ndash507 2015

[104] I V Chikalovets S N Kovalchuk A P Litovchenko V IMolchanova M V Pivkin and O V Chernikov ldquo0 newGalGalNAc-specific lectin from the mussel Mytilus trossulusstructure tissue specificity antimicrobial and antifungal activ-ityrdquo Fish and Shellfish Immunology vol 50 pp 27ndash33 2016

[105] L-J Ling Y-Z Yang and Y-R Bi ldquoExpression and character-ization of two domains of Pinellia ternata agglutinin (PTA) aplant agglutinin from Pinellia ternata with antifungal activityrdquoWorld Journal of Microbiology and Biotechnology vol 26 no 3pp 545ndash554 2010

[106] A J G Simpson and D J McLaren ldquoSchistosoma mansonitegumental damage as a consequence of lectin bindingrdquo Exper-imental Parasitology vol 53 no 1 pp 105ndash116 1982

[107] H Tobata-Kudo H Kudo and I Tada ldquoStrongyloides rattichemokinesis of glycolytic enzyme- and lectin-treated third-stage infective larvae in vitrordquoParasitology International vol 54no 2 pp 147ndash152 2005

[108] C Heim H Hertzberg A Butschi et al ldquoInhibition ofHaemonchus contortus larval development by fungal lectinsrdquoParasites and Vectors vol 8 no 1 article 425 2015

[109] C M L D Melo A L R de Lima E I C Beltrao et alldquoPotential effects of Cramoll 14 lectin on murine Schistosomi-asis mansonirdquo Acta Tropica vol 118 no 2 pp 152ndash158 2011

[110] S R Afonso-Cardoso C V Silva M S Ferreira and M ASouza ldquoEffect of the Synadenium carinatum latex lectin (ScLL)on Leishmania (Leishmania) amazonensis infection in murinemacrophagesrdquo Experimental Parasitology vol 128 no 1 pp 61ndash67 2011

[111] L P D Albuquerque E V Pontual G M D S Santana etal ldquoToxic effects of Microgramma vacciniifolia rhizome lectinon Artemia salina human cells and the schistosomiasis vectorBiomphalaria glabratardquo Acta Tropica vol 138 pp 23ndash27 2014

[112] A F D Santos B S Cavada B A M D Rocha K SD Nascimento and A E G SantrsquoAna ldquoToxicity of someglucosemannose-binding lectins to Biomphalaria glabrata andArtemia salinardquo Bioresource Technology vol 101 no 2 pp 794ndash798 2010

[113] R A Sa N D Santos C S Silva et al ldquoLarvicidal activityof lectins from Myracrodruon urundeuva on Aedes aegyptirdquoComparative Biochemistry and Physiology Part C Toxicology ampPharmacology vol 149 no 3 pp 300ndash306 2009

[114] T H Napoleao E V Pontual T De Albuquerque Lima etal ldquoEffect of Myracrodruon urundeuva leaf lectin on survival


and digestive enzymes of Aedes aegypti larvaerdquo ParasitologyResearch vol 110 no 2 pp 609ndash616 2012

[115] J S Coelho N D L Santos T H Napoleao et al ldquoEffect ofMoringa oleifera lectin on development and mortality of Aedesaegypti larvaerdquo Chemosphere vol 77 no 7 pp 934ndash938 2009

[116] N D L de Santos K S de Moura T H Napoleao etal ldquoOviposition-Stimulant and ovicidal activities of Moringaoleifera lectin on Aedes aegyptirdquo PLOS ONE vol 7 no 9 ArticleID e44840 2012

[117] N D De Lima Santos K Da Silva Paixao T H Napoleaoet al ldquoEvaluation of Moringa oleifera seed lectin in traps forthe capture of Aedes aegypti eggs and adults under semi-fieldconditionsrdquo Parasitology Research vol 113 no 5 pp 1837ndash18422014

[118] A P S deOliveira L L S Silva T A Lima et al ldquoBiotechnolog-ical value ofMoringa oleifera seed cake as source of insecticidallectin againstAedes aegyptirdquo Process Biochemistry vol 51 no 10pp 1683ndash1690 2016

[119] A Jacinto and J V Cordeiro ldquoThe role of transcription-independent damage signals in the initiation of epithelialwound healingrdquo Nature Reviews Molecular Cell Biology vol 14no 4 pp 249ndash262 2013

[120] T Velnar T Bailey andV Smrkolj ldquoThewound healing processan overview of the cellular andmolecular mechanismsrdquo Journalof International Medical Research vol 37 no 5 pp 1528ndash15422009

[121] M Batterbury C A Tebbs JM Rhodes and I Grierson ldquoAgar-icus bisporus (ediblemushroom lectin) inhibits ocular fibroblastproliferation and collagen lattice contractionrdquo Experimental EyeResearch vol 74 no 3 pp 361ndash370 2002

[122] L Yu D G Fernig J A Smith J D Milton and J M RhodesldquoReversible inhibition of proliferation of epithelial cell lines byagaricus bisporus (edible mushroom) lectinrdquo Cancer Researchvol 53 no 19 pp 4627ndash4632 1993

[123] L G Do Nascimento-Neto R F Carneiro S R Da Silva etal ldquoCharacterization of isoforms of the lectin isolated from thered algae Bryothamnion seaforthii and its pro-healing effectrdquoMarine Drugs vol 10 no 9 pp 1936ndash1954 2012

[124] Z Cao N Said S Amin et al ldquoGalectins-3 and -7 but notgalectin-1 play a role in re-epithelialization of woundsrdquo Journalof Biological Chemistry vol 277 no 44 pp 42299ndash42305 2002

[125] N Maaloslashe C Bonde I Laursen M Christiansen and L RHolmich ldquoMannan-binding lectin and healing of a radiation-induced chronic ulcermdasha case report onmannan-binding lectinreplacement therapyrdquo Journal of Plastic Reconstructive andAesthetic Surgery vol 64 no 6 pp e146ndashe148 2011

[126] F Chahud L N Z Ramalho F S Ramalho A Haddad andMC Roque-Barreira ldquoThe lectin KM+ induces corneal epithelialwound healing in rabbitsrdquo International Journal of ExperimentalPathology vol 90 no 2 pp 166ndash173 2009

[127] L G DoNascimento Neto L Da Silva Pinto R M Bastos et alldquoEffect of the lectin of Bauhinia variegata and its recombinantisoform on surgically induced skin wounds in a murine modelrdquoMolecules vol 16 no 11 pp 9298ndash9315 2011

[128] C M L D Melo C S Porto M R Melo Jr et al ldquoHealingactivity induced by Cramoll 14 lectin in healthy and immuno-compromised micerdquo International Journal of Pharmaceuticsvol 408 no 1-2 pp 113ndash119 2011

[129] D D S T Pereira M HM Lima-Ribeiro R Santos-Oliveira etal ldquoTopical application effect of the isolectin hydrogel (Cramoll14) on second-degree burns experimental modelrdquo Journal of

Biomedicine amp Biotechnology vol 2012 Article ID 184538 11pages 2012

[130] V P Brustein F V Souza-Araajo A F M Vaz et al ldquoA novelantimicrobial lectin from Eugenia malaccensis that stimulatescutaneous healing in mice modelrdquo Inflammopharmacology vol20 no 6 pp 315ndash322 2012

[131] M C Coriolano C M L de Melo F D O Silva et al ldquoParkiapendula seed lectin potential use to treat cutaneous wounds inhealthy and immunocompromised micerdquo Applied Biochemistryand Biotechnology vol 172 no 5 pp 2682ndash2693 2014

[132] H Nagase R Visse and G Murphy ldquoStructure and func-tion of matrix metalloproteinases and TIMPsrdquo CardiovascularResearch vol 69 no 3 pp 562ndash573 2006

[133] H Bakowsky T Richter C Kneuer et al ldquoAdhesion charac-teristics and stability assessment of lectin-modified liposomesfor site-specific drug deliveryrdquo Biochimica et Biophysica ActamdashBiomembranes vol 1778 no 1 pp 242ndash249 2008

[134] D L Wise Handbook of Pharmaceutical Controlled ReleaseTechnology Marcel Dekker New York NY USA 2000

[135] C-M Lehr ldquoLectin-mediated drug delivery the second gener-ation of bioadhesivesrdquo Journal of Controlled Release vol 65 no1-2 pp 19ndash29 2000

[136] C Bies C-M Lehr and J F Woodley ldquoLectin-mediated drugtargeting history and applicationsrdquo Advanced Drug DeliveryReviews vol 56 no 4 pp 425ndash435 2004

[137] L Illum ldquoNasal drug deliverymdashpossibilities problems andsolutionsrdquo Journal of Controlled Release vol 87 no 1-3 pp 187ndash198 2003

[138] K H Leong L Y Chung M I Noordin Y Onuki M Mor-ishita andK Takayama ldquoLectin-functionalized carboxymethy-lated kappa-carrageenan microparticles for oral insulin deliv-eryrdquo Carbohydrate Polymers vol 86 no 2 pp 555ndash565 2011

[139] L Neutsch E-M Wirth S Spijker et al ldquoSynergistic tar-getingprodrug strategies for intravesical drug delivery-lectin-modified PLGAmicroparticles enhance cytotoxicity of stearoylgemcitabine by contact-dependent transferrdquo Journal of Con-trolled Release vol 169 no 1-2 pp 62ndash72 2013

[140] Y Yin D Chen M Qiao Z Lu and H Hu ldquoPreparation andevaluation of lectin-conjugated PLGA nanoparticles for oraldelivery of thymopentinrdquo Journal of Controlled Release vol 116no 3 pp 337ndash345 2006

[141] Y Sheng H He and H Zou ldquoPoly(lactic acid) nanoparticlescoated with combined WGA and water-soluble chitosan formucosal delivery of 120573-galactosidaserdquo Drug Delivery vol 21 no5 pp 370ndash378 2014

[142] S K Jain M Gupta A K Sahoo A N Pandey and A K JainldquoLectin conjugated gastro-retentivemicrospheres of amoxicillinfor effective treatment of Helicobacter pylorirdquo Current Sciencevol 106 no 2 pp 267ndash276 2014

[143] A O Adebisi and B R Conway ldquoLectin-conjugated micro-spheres for eradication of Helicobacter pylori infection andinteractionwithmucusrdquo International Journal of Pharmaceuticsvol 470 no 1-2 pp 28ndash40 2014

[144] M R El-Aassar E E Hafez N M El-Deeb and M MG Fouda ldquoMicroencapsulation of lectin anti-cancer agentand controlled release by alginate beads biosafety approachrdquoInternational Journal of Biological Macromolecules vol 69 pp88ndash94 2014

[145] WAcosta J AyalaM CDolan andC L Cramer ldquoRTBLectina novel receptor-independent delivery system for lysosomalenzyme replacement therapiesrdquo Scientific Reports vol 5 ArticleID 14144 2015


[146] K Ikemoto K Shimizu K Ohashi Y Takeuchi M Shimizuand N Oku ldquoBauhinia purprea agglutinin-modified liposomesfor human prostate cancer treatmentrdquo Cancer Science vol 107no 1 pp 53ndash59 2016

[147] S A Svarovsky and L Joshi ldquoCancer glycan biomarkers andtheir detectionmdashpast present and futurerdquo Analytical Methodsvol 6 no 12 pp 3918ndash3936 2014

[148] M Stuchlova Horynova M Raska H Clausen and J NovakldquoAberrant O-glycosylation and anti-glycan antibodies in anautoimmune disease IgA nephropathy and breast adenocarci-nomardquo Cellular and Molecular Life Sciences vol 70 no 5 pp829ndash839 2013

[149] R Goulabchand T Vincent F Batteux J-F Eliaou and P Guil-pain ldquoImpact of autoantibody glycosylation in autoimmunediseasesrdquo Autoimmunity Reviews vol 13 no 7 pp 742ndash7502014

[150] J Roth ldquoLectins for histochemical demonstration of glycansrdquoHistochemistry and Cell Biology vol 136 no 2 pp 117ndash130 2011

[151] E I C Beltrao M T S Correia J Figueredo-Silva and L C BB Coelho ldquoBinding evaluation of isoform 1 fromCratylia mollislectin to human mammary tissuesrdquo Applied Biochemistry andBiotechnologymdashPart A Enzyme Engineering and Biotechnologyvol 74 no 3 pp 125ndash134 1998

[152] M V Dwek H A Ross A J Streets et al ldquoHelix pomatiaagglutinin lectin-binding oligosaccharides of aggressive breastcancerrdquo International Journal of Cancer vol 95 no 2 pp 79ndash85 2001

[153] A Thies I Moll J Berger and U Schumacher ldquoLectin bindingto cutaneous malignant melanoma HPA is associated withmetastasis formationrdquo British Journal of Cancer vol 84 no 6pp 819ndash823 2001

[154] B Schnegelsberg U Schumacher and U Valentiner ldquoLectinhistochemistry of metastasizing and non-metastasizing breastand colon cancer cellsrdquo Anticancer Research vol 31 no 5 pp1589ndash1597 2011

[155] E I C Beltrao P L Medeiros O G Rodrigues et al ldquoParkiapendula lectin as histochemistry marker for meningothelialtumourrdquo European Journal of Histochemistry vol 47 no 2 pp139ndash142 2003

[156] K Blonski K Milde-Langosch A-M Bamberger et al ldquoUlexeuropeus agglutinin-I binding as a potential prognostic markerin ovarian cancerrdquo Anticancer Research vol 27 no 4 pp 2785ndash2790 2007

[157] S Korourian E Siegel T Kieber-Emmons and B Monzavi-Karbassi ldquoExpression analysis of carbohydrate antigens inductal carcinoma in situ of the breast by lectin histochemistryrdquoBMC Cancer vol 8 article 136 2008

[158] C Oliveira J A Teixeira F Schmitt and L Domingues ldquoAcomparative study of recombinant and native frutalin bindingto human prostate tissuesrdquoBMCBiotechnology vol 9 article 782009

[159] F-L Wang S-X Cui L-P Sun et al ldquoHigh expression of 1205722 3-linked sialic acid residues is associated with the metastaticpotential of human gastric cancerrdquoCancer Epidemiology vol 32no 5-6 pp 437ndash443 2009

[160] A P V Sobral M J B M Rego C L B Cavalacanti L BCarvalho Jr and E I C Beltrao ldquoConA and UEA-I lectinhistochemistry of parotid gland mucoepidermoid carcinomardquoJournal of Oral Science vol 52 no 1 pp 49ndash54 2010

[161] A F G Leal N E P Lopes A T R Clark N T De PontesFilho E I C Beltrao and R P Neves ldquoCarbohydrate profiling

of fungal cell wall surface glycoconjugates of Aspergillus speciesin brain and lung tissues using lectin histochemistryrdquo MedicalMycology vol 50 no 7 pp 756ndash759 2012

[162] C G Andrade P E C Filho D P L Tenorio et al ldquoEvaluationof glycophenotype in breast cancer by quantum dot-lectinhistochemistryrdquo International Journal of Nanomedicine vol 8pp 4623ndash4629 2013

[163] K Chandler and R Goldman ldquoGlycoprotein disease markersand single protein-omicsrdquo Molecular and Cellular Proteomicsvol 12 no 4 pp 836ndash845 2013

[164] P Silva L Coelho and M Correia ldquoElectrochemical biosens-ing strategies to detect serum glycobiomarkersrdquo Advances inResearch vol 6 no 6 pp 1ndash17 2016

[165] E B Bahadir and M K Sezginturk ldquoApplications of com-mercial biosensors in clinical food environmental and bio-threatbiowarfare analysesrdquo Analytical Biochemistry vol 478pp 107ndash120 2015

[166] X Liu P A Duckworth and D K Y Wong ldquoSquare wavevoltammetry versus electrochemical impedance spectroscopyas a rapid detection technique at electrochemical immunosen-sorsrdquo Biosensors and Bioelectronics vol 25 no 6 pp 1467ndash14732010

[167] F Li Y Feng L Yang L Li C Tang and B Tang ldquoAselective novel non-enzyme glucose amperometric biosensorbased on lectin-sugar binding on thionine modified electroderdquoBiosensors and Bioelectronics vol 26 no 5 pp 2489ndash2494 2011

[168] M D L Oliveira M T S Correia and F B Diniz ldquoA novelapproach to classify serum glycoproteins from patients infectedby dengue using electrochemical impedance spectroscopy anal-ysisrdquo Synthetic Metals vol 159 no 21-22 pp 2162ndash2164 2009

[169] D M N Luna M D L Oliveira M L Nogueira and C AS Andrade ldquoBiosensor based on lectin and lipid membranesfor detection of serum glycoproteins in infected patients withdenguerdquoChemistry and Physics of Lipids vol 180 pp 7ndash14 2014

[170] S A Hong J Kwon D Kim and S Yang ldquoA rapid sensitiveand selective electrochemical biosensor with concanavalin Afor the preemptive detection of norovirusrdquo Biosensors andBioelectronics vol 64 pp 338ndash344 2015

[171] T Bertok P Gemeiner M Mikula P Gemeiner and J TkacldquoUltrasensitive impedimetric lectin based biosensor for glyco-proteins containing sialic acidrdquoMicrochimica Acta vol 180 no1-2 pp 151ndash159 2013

[172] T Bertok A Sediva J Katrlik et al ldquoLabel-free detection ofglycoproteins by the lectin biosensor down to attomolar levelusing gold nanoparticlesrdquo Talanta vol 108 pp 11ndash18 2013

[173] T Bertok L Klukova A Sediva et al ldquoUltrasensitive impedi-metric lectin biosensors with efficient antifouling propertiesapplied in glycoprofiling of human serum samplesrdquo AnalyticalChemistry vol 85 no 15 pp 7324ndash7332 2013

[174] M L S Silva E Gutierrez J A Rodrıguez C Gomes andL David ldquoConstruction and validation of a Sambucus nigrabiosensor for cancer-associated STn antigenrdquo Biosensors andBioelectronics vol 57 pp 254ndash261 2014

[175] X Zhang Y Teng Y Fu et al ldquoLectin-based biosensor strategyfor electrochemical assay of glycan expression on living cancercellsrdquoAnalytical Chemistry vol 82 no 22 pp 9455ndash9460 2010

[176] M D L Oliveira M L Nogueira M T S Correia L C BB Coelho and C A S Andrade ldquoDetection of dengue virusserotypes on the surface of gold electrode based on Cratyliamollis lectin affinityrdquo Sensors and Actuators B Chemical vol155 no 2 pp 789ndash795 2011


[177] K Y P S Avelino C A S Andrade C P De Melo et alldquoBiosensor based on hybrid nanocomposite and CramoLLlectin for detection of dengue glycoproteins in real samplesrdquoSynthetic Metals vol 194 pp 102ndash108 2014

[178] E F Fang P Lin J H Wong S W Tsao and T B Ng ldquoAlectin with anti-HIV-1 reverse transcriptase antitumor andnitric oxide inducing activities from seeds of Phaseolus vulgariscv extralong autumn purple beanrdquo Journal of Agricultural andFood Chemistry vol 58 no 4 pp 2221ndash2229 2010

[179] E F Fang W L Pan J H Wong Y S Chan X J Ye and T BNg ldquoA new Phaseolus vulgaris lectin induces selective toxicityon human liver carcinomaHep G2 cellsrdquoArchives of Toxicologyvol 85 no 12 pp 1551ndash1563 2011

[180] S R KabirMM Nabi A Haque R U Zaman Z HMahmudand M A Reza ldquoPea lectin inhibits growth of Ehrlich ascitescarcinoma cells by inducing apoptosis andG2Mcell cycle arrestin vivo in micerdquo Phytomedicine vol 20 no 14 pp 1288ndash12962013

[181] L Wu T Liu Y Xiao et al ldquoPolygonatum odoratum lectininduces apoptosis and autophagy by regulation of microRNA-1290 and microRNA-15a-3p in human lung adenocarcinomaA549 cellsrdquo International Journal of Biological Macromoleculesvol 85 pp 217ndash226 2016

[182] M Deepa T Sureshkumar P K Satheeshkumar and S PriyaldquoPurified mulberry leaf lectin (MLL) induces apoptosis and cellcycle arrest in human breast cancer and colon cancer cellsrdquoChemico-Biological Interactions vol 200 no 1 pp 38ndash44 2012

[183] N Yang D-F Li L Feng et al ldquoStructural basis for the tumorcell apoptosis-inducing activity of an antitumor lectin fromthe edible mushroom Agrocybe aegeritardquo Journal of MolecularBiology vol 387 no 3 pp 694ndash705 2009

[184] R M Araujo A F Vaz J S Aguiar et al ldquoLectin fromCrataevatapia bark exerts antitumor anti-inflammtory and analgesicactivitiesrdquo Natural Products and Bioprospecting vol 1 no 2 pp97ndash100 2011

[185] Y R Li Q H Liu H X Wang and T B Ng ldquoA novellectin with potent antitumor mitogenic and HIV-1 reversetranscriptase inhibitory activities from the edible mushroomPleurotus citrinopileatusrdquo Biochimica et Biophysica Acta vol1780 no 1 pp 51ndash57 2008

[186] G Zhang J Sun H Wang and T B Ng ldquoFirst isolation andcharacterization of a novel lectin with potent antitumor activityfrom a Russula mushroomrdquo Phytomedicine vol 17 no 10 pp775ndash781 2010

[187] C A S Andrade M T S Correia L C B B CoelhoS C Nascimento and N S Santos-Magalhaes ldquoAntitumoractivity of Cratylia mollis lectin encapsulated into liposomesrdquoInternational Journal of Pharmaceutics vol 278 no 2 pp 435ndash445 2004

[188] J Y Taek C Y Yung B K Tae et al ldquoAntitumor activityof the Korean mistletoe lectin is attributed to activation ofmacrophages andNKcellsrdquoArchives of Pharmacal Research vol26 no 10 pp 861ndash867 2003

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


T cell

Lectin

Mitogenicactivation

Receptor

(a)

T cell Naive CD4+

Th 1

Th 2

Th 17

CD8 T cell

NK cell

Macrophage

Eosinophil

B cell

Mast cell

Tissue immunity

(b)

Figure 1 Lectins induced in vitro mitogenic activation of T cells (a) and stimulated in vivoTh1 Th2 andTh17 responses (b)

host cells resulting in the virus entrance into cell [30] Sialicacid-specific lectins such as influenza virus hemagglutininwere used to search antiviral drugs and inhibitors that canremove or block the sialic acid site in host cells in orderto prevent the binding [31] Lectins from bacteria play arole in the bacterial virulence through the binding betweenbacterial lectins and specific carbohydrate moieties of hostcells being an important factor for recognition and adhesion[32 33] Strong anti-HIV (human immunodeficiency virus)activity in vitro has been described to bacterial lectins [34ndash36] Various fungal lectins distributed among mushroomsmicrofungi and yeasts exhibited many physiological effectsand biomedical applications Similar to bacterial lectins theinteraction between fungal lectins and host glycans has animportant role in the infection process of fungi [37] Fungallectins revealed immunomodulatory mitogenic antiprolif-erative antitumoral antiviral and antimicrobial activities[5 38]

A large number of algal lectins have also attractedconsiderable attention for biomedical applications includinganti-HIV antitumoral antimicrobial anti-inflammatory andantinociceptive activities [39] Animal lectins play a rolein various physiological processes such as metastasis ofcancer apoptosis pathways and immunomodulation [40 41]Many lectins isolated from animal tissues were investigatedas apoptotic agents immunomodulatory antiviral therapyand anticancer drug targets [41 42] Plant lectins purifiedand characterized from distinct plant families and tissuesincluding seeds barks leaves roots fruits and flowersexhibited various molecular features structures and carbo-hydrate specificities [43] The Leguminosae family has thelargest group of well-characterized legume lectins which areinteresting due to a variety of carbohydrate specificity andgreater availability in nature [44] In general a wide rangeof biological applications has been attributed to plant lectinssuch as mediators of inflammatory and immune responseantiviral antibacterial antifungal and antihelminthic agentshealing effect drug delivery histochemical markers biosens-ing of diseases and antitumoral activities [3 45 46] Thisreview discusses representative lectins from distinct naturalsources highlighting some biological effects in vivo andin vitro and their potential for diagnosis and therapeuticapplications

2 Lectin Induced Mechanisms ofImmunological and InflammatoryResponses

Immunological and inflammatory responses play a role inthe protection of an organism against an invasive agentand transformed cells The immune system acts throughtwo ways known as innate and adaptive immune responsesactivated by a group of cells and molecules that promotethe inactivation or destruction of aggressive agent [47]There are neutrophils eosinophils basophils and mono-cytesmacrophages with specific functions and ability toproduce and release molecules named cytokines whichmodulate the activation of immune cells inflammation andhumoral response The search for biomolecules that canmodulate (up or down) mechanisms of immune responseis attractive for adjustment of immune conditions andtherapeutic applications in diverse immune response-relateddiseases and infections

Several lectins from distinct sources showed immuno-modulatory effects such as mitogenic activity (Figure 1(a))and induction of T helper type 1 (Th1) type 2 (Th2) ortype 17 (Th17) responses (Figure 1(b)) The pivotal step tostart immunomodulatory activities of lectins is the binding oflectins to glycans targets on cell surface which have the role oflectin-receptors [48] Lectin binding can induce the immuneresponse through mediators such as second messengersreleased from themembrane For example diacylglycerol andinositol 145-triphosphate generated through the hydrolysisof phosphatidylinositol 45-diphosphate increase in cytoso-lic Ca2+ levels release of cytokines specifics binding toreceptors distributed in stimulatory regions or domainscascade started by linkage to TCR receptor and further othermechanisms incompletely elucidated [49 50]

Fungal lectins have been highlighted as potent modu-lators of immune response TML-1 and TML-2 are lectinsfrom the mushroom Tricholoma mongolicum which inducedthe Th1 response through the activation of macrophagesfrom lectin-treated mice and stimulated the production ofnitrite ion and cytokine tumor necrosis factor (TNF) bymacrophages Additionally both lectins promoted in vivoactivation of mouse macrophages triggering the inhibitionof tumor cell growth [51] These effects may result from





















































(a) (b)

(c) (d)








ICM

ECM

Normal mucin

Lectin

(a)

Lectin

ICM

ECM


(b)


ECM

ICM

Lectin


Drug







Normal tissue

conjugated lectin

Hydrogen peroxide

Oxidated DAB

Peroxidase-

Peroxidase




DAB





























ElectrodeElectrode

Lectin Glycoprotein

Glycan Cell

E (V)

I(휇

A)

EIS DPV

I(휇

A)

E (V)EIS DPV

A

B

A

B

A㰀

B㰀

(a) (b)



Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Z㰀㰀

(Ω)

Z㰀㰀 (Ω)






















Agrocybe aegerita



[9]





[11 12]
















9 Conclusions




Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




































































(a) (b)

(c) (d)








ICM

ECM

Normal mucin

Lectin

(a)

Lectin

ICM

ECM


(b)


ECM

ICM

Lectin


Drug







Normal tissue

conjugated lectin

Hydrogen peroxide

Oxidated DAB

Peroxidase-

Peroxidase




DAB





























ElectrodeElectrode

Lectin Glycoprotein

Glycan Cell

E (V)

I(휇

A)

EIS DPV

I(휇

A)

E (V)EIS DPV

A

B

A

B

A㰀

B㰀

(a) (b)



Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Z㰀㰀

(Ω)

Z㰀㰀 (Ω)






















Agrocybe aegerita



[9]





[11 12]
















9 Conclusions




Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















ICM

ECM

Normal mucin

Lectin

(a)

Lectin

ICM

ECM


(b)


ECM

ICM

Lectin


Drug







Normal tissue

conjugated lectin

Hydrogen peroxide

Oxidated DAB

Peroxidase-

Peroxidase




DAB





























ElectrodeElectrode

Lectin Glycoprotein

Glycan Cell

E (V)

I(휇

A)

EIS DPV

I(휇

A)

E (V)EIS DPV

A

B

A

B

A㰀

B㰀

(a) (b)



Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Z㰀㰀

(Ω)

Z㰀㰀 (Ω)






















Agrocybe aegerita



[9]





[11 12]
















9 Conclusions




Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Normal tissue

conjugated lectin

Hydrogen peroxide

Oxidated DAB

Peroxidase-

Peroxidase




DAB





























ElectrodeElectrode

Lectin Glycoprotein

Glycan Cell

E (V)

I(휇

A)

EIS DPV

I(휇

A)

E (V)EIS DPV

A

B

A

B

A㰀

B㰀

(a) (b)



Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Z㰀㰀

(Ω)

Z㰀㰀 (Ω)






















Agrocybe aegerita



[9]





[11 12]
















9 Conclusions




Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





































ElectrodeElectrode

Lectin Glycoprotein

Glycan Cell

E (V)

I(휇

A)

EIS DPV

I(휇

A)

E (V)EIS DPV

A

B

A

B

A㰀

B㰀

(a) (b)



Z㰀㰀

(Ω)

Z㰀㰀 (Ω)

Z㰀㰀

(Ω)

Z㰀㰀 (Ω)






















Agrocybe aegerita



[9]





[11 12]
















9 Conclusions




Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
































Agrocybe aegerita



[9]





[11 12]
















9 Conclusions




Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















Competing Interests


Acknowledgments


References













































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




































































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















lectins, interconnecting proteins with biotechnological ...2. lectin induced mechanisms of...

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