antitumoral lung_ecam,v.2014,article id 604152,15pages

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Review ArticleMedicinal Plants and Other Living Organisms with AntitumorPotential against Lung Cancer

Luara de Sousa Monteiro, Katherine Xavier Bastos,

José Maria Barbosa-Filho, Petrônio Filgueiras de Athayde-Filho, Margareth de Fátima

Formiga Melo Diniz, and Marianna Vieira Sobral

Department of Pharmaceutical Sciences, Federal University of Paraiba, - João Pessoa, PB, Brazil

Correspondence should be addressed to Marianna Vieira Sobral; [email protected]

Received April ; Revised July ; Accepted July ; Published July

Academic Editor: Tomas Efferth

Copyright © Luara de Sousa Monteiro et al. Tis is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Lung cancer is a disease with high morbidity and mortality rates. As a result, it is ofen associated with a signicant amount o suffering and a general decrease in the quality o lie. Herbal medicines are recognized as an attractive approach to lung cancertherapy with littleside effectsand area majorsource o newdrugs.Te aimo this work wasto review themedicinal plants andotherliving organismswith antitumor potential against lung cancer. Te assays wereconducted with animals and humans, and Lewis lung

carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopiawere the countries that most publishedstudies o species with antitumor activity. O the plants evaluated, demonstrated antitumor activity. In addition, six other livingorganisms were cited or antitumor activity against lung cancer. Mechanisms o action, combination with chemotherapeutic drugs,and new technologies to increase activity and reduce the toxicity o the treatment are discussed. Tis review was based on theNAPRALER databank, Web o Science, and Chemical Abstracts. Tis work shows that natural products rom plants continue tobe a rich source o herbal medicines or biologically active compounds against cancer.

1. Introduction

Cancer is a collection o heterogeneous genetic diseasesunited by common alterations in multiple cellular signaling

pathways []. Various hallmarks have been proposed orcancer cells. Evasion o programmed cell death or apoptosishas been recognized as one o the main alterations thatdictate malignant growth []. Furthermore, other eaturesinclude sel-sufficiency in growth signaling, deregulationo cellular energetics, sustained angiogenesis, evasion o immune detection, and tissue invasion and metastasis [–]. In addition, two characteristics o cancer that acilitateacquisition o these hallmarks have been described: genomeinstability and mutation tumor-promoting inammation [].Coordinated processes such as cell prolieration, differentia-tion, and apoptosis are modied, producing altered cellularphenotypes with these specic characteristics [, ].

According to the World Health Organization (WHO),cancer represents noncommunicable diseases responsible or% o deaths worldwide, where it is characterized as the sec-ond cause o death in western countries [, ]. Its incidence is

strongly affected by demographic aspects, such as populationaging, eating habits, and, in particular, environmental actorssuch as exposure to ultraviolet rays. Te International Agency or Research on Cancer (IARC) estimates that there were .million new cancer cases in and that this number isexpected to grow to . million by [, ].

Lung cancer is currently the malignant tumor with thehighest mortality rate worldwide, ofen because it is notdetected until there has been substantial progression o theillness, which leads to a signicant reduction in quality o lieo the patient []. Different actors are pointed out as possiblecauses o lung cancer, including active cigarette smoking,exposure to secondhand cigarette smoke (passive smoking),

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2014, Article ID 604152, 15 pageshttp://dx.doi.org/10.1155/2014/604152

http://dx.doi.org/10.1155/2014/604152http://dx.doi.org/10.1155/2014/604152


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Evidence-Based Complementary and Alternative Medicine

pipe and cigar smoking, exposure to indoor and outdoor airpollution, exposure to radiation, and occupational exposureto agents such as asbestos, nickel, chromium, and arsenic[]. Te most important risk actor is smoking [] and theincidence rates o lung cancer are generally higher amongmen than women []. Lung cancer is classied into nons-

mall cell lung carcinoma (NSCLC), including squamous cellcarcinoma, adenocarcinoma, and large cell carcinoma, whichrepresents % o all lung cancer cases, and the remainingcases are small cell lung carcinoma (SCLC) [, ]. Recently,a new classication was published that dened “molecularsubtypes” o lung cancer based on specic actionable geneticaberrations []. Many strategies have been studied or lungcancer chemoprevention and treatment, including SApathway inhibition (e.g., curcumin), cell-cycle arrest (e.g.,gambogenic acid), hER silencing, miRNA modulation,iNOS suppression, chitin inhibition, angiotensin receptorblockade, GF- antagonism, VEGFR-/EGFR inhibition(e.g., vandetanib), and Nr activation []. Some strategieshave been proven effective in human trials, or example, theuse o ceritinib, a new ALK (anaplastic lymphoma kinasegene) inhibitor, in patients with advanced lung cancersharboring genetic alterations in ALK, in a phase study []. In addition, the study o tumor-associated biomarkershas grown with the aim o reducing the mortality rate o lung cancer by early diagnosis and prognosis []. Anotherapproach that has been studied is the use o the cancerstem cell model, which offers new insights into the limita-tions o current cancer treatments []. New opportunitiesor targeted therapy are under development based on thediscovery o multiple molecular mechanisms underlyingthe development, progression, and prognosis o lung can-cer. Among them, the targeted inhibition o the vascularendothelial growth actor (VEGF) or epidermal growth actor(EGF) signaling pathways has been clinically validated in thetreatment o advanced NSCLC [].

Nowadays, surgery, chemotherapy, radiation, hormones,and immunotherapy are the main approaches or the cancertreatment, ofen supplemented by other complementary andalternative therapies, such as herbal medicines. Althoughchemotherapy is the method most used, several problemsare associated with its use, including limited efficacy, severetoxicity, and multidrug resistance [].

Plants have a long history o use in the treatment o cancer and continue to be a major source o new drugs[]. Herbal medicines have been recognized as one o the

attractive approaches or lung cancer therapy because they have proven to be useul and effective in sensitizing conven-tional agents, prolonging patient survival time, preventingside effects o chemotherapy, and improving quality o liein lung cancer patients []. A recent cohort study with cancer patients revealed that the percentage o patientsusing herbal medicines in combination with conventionalchemotherapy was approximately % []. In these cases,natural products as complementary therapy or the treatmento lung cancer were used mainly with the aim o reducingtoxicity, alleviating cancer-related symptoms, stimulating theimmune system, and even having direct anticancer effects[].

Many natural products or synthetic analogs are stillwidely used clinically, or example, the so-called vinca alka-loids, vinblastine and vincristine, isolated rom the Mada-gascar periwinkle, Catharanthus roseus, paclitaxel (axol),obtained rom the leaves o various axus species, andthe two clinically active agents, etoposide and teniposide,

which are semisynthetic derivatives o the natural productepipodophyllotoxin []. Other promising agents, naturalor synthetic analogs, are in the clinical development phase,including avopiridol [] and combretastatin A []. Inaddition, many compounds obtained rom plants or otherliving organisms, alone or in combination, are still studied by in vitro models or determining their mechanisms o actionagainst lung cancer cells [–].

Te most common orms o therapeutic use o plantsworldwide are teas and herbal inusions. Considering thattheir use has increased in recent years aiming to reducethe risks o cardiovascular disease and cancers, research isgoing on to characterize this effect. Recent data showedthat different teas and herbal inusions widely consumed inHong Kong, Macau, aiwan, Mainland China, and many other places in the world have antiprolierative effects againsthuman lung cancer cells []. Many cancer patients takethese medicines, but their effects at the cellular level arelargely unknown. However, different preclinical and clinicalstudies have shown the antitumor activity o herbal extractsagainst lung cancer []. Te data have shown that inductiono apoptosis is the major mechanism o action o theseextracts. Te majority o the articles show the effect o Chinese herbal extracts.Some o them show that the responseo lung tumor cells to these extracts was similar to theirresponse to conventional chemotherapeutic drugs, and thattheir mechanism o action was associated with apoptosisinduction []. Some examples o medicinal herbs withantitumor activity against lung cancer cells can be cited.Selaginella tamariscina is a traditional Chinese herb withantimetastatic effects in vitro and in vivo against lung cancercells []. Crocus sativus L. (Saffron) aqueous extract is widely used as a ood additive and in traditional medicine or cancer.Its effects against lung cancer cells were investigated, andantilung cancer activity was associated with induction o apoptosis []. Te bioactive raction o oona sinensis leavesinhibited H xenograf tumor growth in both therapeuticand preventive experiments. An in vitro study revealedthat the natural product acts by inducing apoptosis [].Te methanolic raction o Sesbania grandiora was ound

to exert potent antiprolierative effects especially againsthuman lung cancer cell lines. Tis effect was related tothe induction o apoptosis associated with high levels o reactive oxygen species (ROS) intermediates []. A study o the combination o active components o Prunella revealedthat total triterpenes and total phenols had antilung canceractivity and thattheir combination signicantly enhanced theactivity. Tus, its efficacy against lung cancer was attributableto multiple components acting at an optimal ratio [].Descurainia sophia has been traditionally used in Koreanmedicine. Recent data rom the study o gene expressionprole ound the antitumor effect o the ethanol extract o the seeds o D. sophia against lung cancer to be involved with


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the regulation o metabolism- and signaling-related pathways[]. Mountain ginseng butanol extract inhibited lung cancercell growth by inducing apoptosis. Its mechanisms wereassociated with a reduction in NF-B activity and increase inp activity [].

Substances isolated rom various medicinal plants have

also been extensively studied or their antilung cancer activ-ity. [6]-Gingerol, a pungent ingredient o ginger (Zingiber officinale) showed antiangiogenic activity in vitro and invivo and reduced the number o lung metastases in micereceiving BF melanoma cells []. Embelin, an activecomponent o ruits o Embelia ribes, has been demonstratedto possess a broad spectrum o therapeutic properties, includ-ing antitumor activity against lung cancer cells. Recent dataindicate the crucial role o p and JNK pathways in embelin-induced apoptosis []. Danshen (Salvia miltiorrhiza Bunge)is a traditional medicine that has been used in China totreat various diseases, including cancer. anshinone I is aditerpene isolated rom this species, which reduced lungadenocarcinoma tumor growth. Te studies o its mecha-nisms showed that the compound inhibits pulmonary tumorormation in an animal model by downregulation o the cellcycle atS and G/M phases []. A carbazole alkaloid isolatedrom Murraya koenigii Spreng, girinimbine, inhibited lungcancer cell growth by inducing both intrinsic and extrinsicpathways o apoptosis []. Capilliposide, extracted rom atraditional Chinese medicine, Lysimachia capillipes, inducedapoptosis in NSCLC cells. Xenograf tumor growth wassignicantly decreased afer in vivo treatment. Te in vitrodata revealed that capilliposide increased the intracellularlevel o ROS, which activated the mitochondrial apoptoticpathway []. Scutellaria baicalensis root is used in China asan adjuvant in the chemotherapy o lung cancer. Recently,three compounds were associated with its activity, baicalin,baicalein, and wogonin []. Subamolide A, isolated romCinnamomum subavenium, induced lung cancer cell death by ROS generation, which triggers mitotic catastrophe ollowedby apoptosis []. erpinen--ol, a monoterpene componento the essential oils o several aromatic plants, showed itsantitumor effect on NSCLC cells by induction o apoptosis,with involvement o the mitochondrial apoptotic pathway []. Davallic acid is the major active compound o Davalliadivaricata, a species traditionally employed in olk medicineor the therapy o lung cancer in aiwan. Recent data showedthat this compound induced oxidative stress and apoptosisin lung cancer cells []. otal avonoids o Daphne genkwa

inhibited tumor growth and metastasis by protecting the via-bility o host immunocytes and their prolieration potentialand selectively inhibiting tumor cell prolieration. In thisraction, daphnodorin B was the predominant constituent[].

In addition, many studies have shown the use o com-bined therapy o herbal medicines or natural substances withchemotherapeutic drugs to enhance their antitumor effectsand/or reduce their toxicity. Te combination o Xiao-Ai-Ping, a traditional Chinese medicine, and cisplatin promotesthe inltration and unction o CD+ cells and thusenhances the growth-inhibitory effects o cisplatin on LLCxenografs []. Marsdenia tenacissima has long been used

as a remedy to treat cancer in China. Its combination withgetinib, an orally active tyrosine kinase inhibitor, improvedgetinib efficacy in NSCLC regardless o EGFR status[, ].Te combined therapy o plants extracts, Phyllanthus emblicaand erminalia bellerica, with doxorubicin or cisplatinresulted in a synergistic effect and the possibility o reducing

the doses o the chemotherapeutic drugs []. FuzhengFangai pill (FZFA), a traditional Chinese ormula, is widely used or cancer treatment. Recent studies showed that FZFAcombined with cyclophosphamide (CX) strongly reducedthe growth and metastatic rate o LLC through inhibitiono the SOCS/JAK-SA pathway and inammatory cytokineresponses. In addition, it was observed that the combinationhad greater activity than CX alone []. Osthole is a naturalcompound extracted rom a number o medicinal plants.Te combination o osthole and cisplatin, one o the mostactive chemotherapeutic agents in lung cancer treatment,resulted in greater efficacy in growth inhibition andapoptosisinduction []. Meta-analysis o randomized trials showedthat Astragalus-based Chinese herbal medicine may increasethe effectiveness o platinum-based chemotherapy whencombined with chemotherapy []. A clinical study showedthat the combination o Chinese drugs and conventionalchemotherapy in NSCLC patients can enhance short-termtherapeutic efficacy in the treatment o NSCLC and prolongpatients’ median survival time, but it did not nd any evidentimpact on median time to progression [].

New technologies are in development to enhance theactivity and reduce the toxicity o natural products duringthe research o new therapies. Liposomes may be a promisingdelivery system or drugs in cancer treatment, including lungcancer []. Te development o liposome-based cisplatindrug called Lipoplatin was benecial in reducing the nephro-toxicity o cisplatin, the drug o choice or the treatmento NSCLC. Lipoplatin is anticipated to complete phase IIIclinical trial testing in and []. -elemene, asesquiterpene vinyl monomer isolated rst rom Curcumawenyujin (Zingiberaceae) rhizome, is present in Chineseherbs and plants. Different studies with this compound haveshown efficient antilung cancer activity including inhibit-ing angiogenesis, inducing tumor cell apoptosis, enhancingradiosensitivity, and avorable chemotherapeutic effects incombination with other anticancer agents. In addition, -elemene has only slight side effects. However, the clinicalapplication o -elemene was limited by its hydrophobicproperty, poor stability, and low bioavailability. Phase II

clinical trials with -elemene are in development, and aimingto improve o its pharmacokinetics new delivery systemsare being produced, including liposome-based delivery sys-tems o -elemene. Te authors emphasize that -elemeneliposomes will be critical or uture clinical applications o -elemene in lung cancer treatment []. Herbal extractshave also been studied using new technologies. Te ethano-lic extract o Polygala senega (EEPS) caused apoptosis inlung cancer cell line A. Its poly-(lactic-co-glycolic) acid(PLGA) nanoparticle-encapsulated orm enhanced cellularentry and bioavailability and inhibited the growth o lungcancer cells better than EEPS. Te apoptosis o A cellswas associated with decreased expression o survivin and


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8/16




n a m e

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Te extract o the lichen Cladonia leptoclada showed sig-nicant inhibitory activity against LLC in mice. In this study,an active extract was ractionated, and the principal tumor-inhibitory constituent was characterized and identied as l-usnic acid [].

Extracts o mistletoe (commercial sample o Viscum

album lea and stem) have been used or medicinal purposesor several centuries and are known to contain alkaloids withcytotoxic effects in vitro and in vivo []. Te administrationo mistletoe induced tumor growth inhibition and reduc-tion o metastases, associated with immunomodulation. Teauthors reported that although lectins represent a class o active components studied o mistletoe origin, it is notlikely that they alone are responsible or all effects o theplant extracts [, ]. A randomized phase II study o mistletoe combined with carboplatin-containing regimenswas conducted in advanced NSCLC patients. No effects onquality o lie or total adverse events were seen. Nevertheless,chemotherapy dose reductions, severe nonhaematologicalside effects, andhospitalizations were less requent in patientstreated with mistletoe, warranting urther investigation as amodier o chemotherapy-related toxicity []. In anotherstudy, a patient with SCLS was treated initially with extractso mistletoe and homoeopathic treatment and appearedto respond. Subsequently, radiotherapy was given and thepatient lived or ve years and seven months []. Accordingto the authors, the acknowledgment o the Viscum albumextract as a phytotherapeutic adjuvant may lead to its usetogether with othertreatments in advanced cancer biotherapy [, ].

Different ractions derived rom the unicellular greenalga Chlorella vulgaris, strain CK, were tested in relationto antitumor activity against lung cancer. Te most activeraction consisted o galactose-rich carbohydrate (.%) andprotein (.%), suggesting that the protein moiety o theglycoprotein is mainly related to the expression o antilungcancer activity [].

A studywith Phellinus linteus showed thatthe polysaccha-ride raction inhibited tumor growth in NCI-H-implantedmice and reduced the requency o pulmonary metastasiso BF melanoma. Also studied was combination therapy with the polysaccharide raction and Adriamycin. Althoughthe combination was more effective in inhibiting tumorgrowth, this effect was not observed on the metastases [].

Garlic ( Alliumsativum) isa common plant used mainly asa ood, and it is a medicinal herb commonly used worldwide.

Te aged garlic extract (AGE) inhibited the growth o LL/lungcarcinoma (syngeneic)cells transplanted intomice.AGEstimulated the prolieration o mouse spleen cells and therelease o cytokines, increased NK activities, and enhancedphagocytosis by peritoneal macrophages. AGE treatmentalso stimulated the reactivity o lymphocytes in responseto cytokines or mitogens. Tereore, it was observed thatthe immunostimulant effect was associated with antitumoractivity [, ].

A clinical assay showed that treatment with Chelidoniummajus (preparation Ukrain) in nine men with histologically proven lungcancer, previously untreated, induced an increasein the proportion o total -cells and a signicant decrease

in the percentage o -suppressor cells. Te restoration o cellular immunity was accompanied by an improvement inthe clinical course o the disease. Tis effect was partic-ularly pronounced in patients who responded to urtherchemotherapy. Te authors concluded that Ukrain can beimmunologically effective in lung cancer patients and can

improve cellular immune response [].Te in vivo antitumor effect o a raction o an ethanolicextract o Nigella sativa seeds was studied on LLC-implanted(s.c.) mice. Tis raction prolonged the lie span o the miceand produced signicant tumor inhibition. Alpha-hederin, atriterpene saponin, was obtained rom this raction, whichinduced signicant dose-dependent tumor inhibition, sug-gesting that the activity is related to the presence o this com-pound. However, the underlying mechanism(s) o antitumoractivity o alpha-hederin remains to be established [].

Te stems and roots o Schisandra propinqua are amajor component o the Manshanxiang Complex, a herbalmedicine preparation used or the treatment o lung car-cinoma in several hospitals o Yunnan Province in China[]. In addition, the water extract rom the stems androots o S. propinqua shows activity against LLC in animaltests []. Te triterpenoid manwuweizic acid, isolated romits alcoholic extract, exhibited signicant inhibitory activity against LLC, suggesting that this compound is probably amajor anticancer active principle o the plant [, ].

Review articles about the chemical properties, thera-peutic benets, and toxicity o Withania somnifera (ashwa-gandha, WS), one o the most important herbs o Ayurveda(the traditional system o medicine in India), have beenpublished. Te antitumor activity was described in differentin vitro and in vivo experimental models, including urethane-induced lung adenoma in mice. Te data showed that theethanol extract o W. somnifera signicantly reduced tumorincidence. In addition to providing protection rom carcino-genic effects, the treatment also reversed the adverse effects o urethane on total leukocyte count, lymphocyte count, body weight, and mortality [, ].

Current studies have demonstrated that green teapolyphenols, obtained rom Camellia sinensis, are powerulantioxidants with anticarcinogenic properties. Te primary catechins in green tea are epicatechin, epicatechin--gallate,epigallocatechin, and epigallocatechin--gallate. A clinicalstudy investigated the chemopreventive effects o green teaand coffee among cigarette smokers. Te results suggest thatgreen tea polyphenols may have an anitmutagenic effect

against smoke-induced mutations in humans by blockingthe cigarette-induced increase in sister-chromatid exchangerequency. It has also been shown that cultured human lungcells (A) pretreated with green tea polyphenols and thenexposed to a cigarette smoke solution or H

2O

2 had a reduced

incidence o DNA strand breaks. Pretreatment with greentea polyphenols also reduced the overall toxicity o H

2O

2

as determined by cell growth afer exposure. Tese resultssuggest that green tea polyphenols may inhibit DNA damageand other mutations in cells exposed to oxidants and that thiseffect is associated with anticarcinogenic properties []. Arecent article published evidence rom epidemiologic studieson cancer prevention by green tea. Various epidemiologic


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studies have examined the association between green teaconsumption and lung cancer risk. Te inconsistent resultso those studies could be partly a result o the potentialconounding effect o smoking. Te data revealed that theprotective effect o green tea consumption on lung cancerrisk was conned to nonsmokers [].

Te effects o black tea obtained rom C. sinensis werealso studied. Te administration o black tea polyphe-nols through the drinking water signicantly inhibited-(methylnitrosamino)--(-pyridyl)-l-butanone (NNK) andinduced early bronchial cell prolieration in the short-term model. In long-term studies, administration o black tea, afer a single dose o NNK, inhibited the progres-sion o adenoma to adenocarcinoma. Te cell prolier-ation rate in adenomas was also suppressed by black tea treatment. Te authors related that such activities, atthe early and late stages o lung tumorigenesis, may beimportant or the cancer-chemopreventive activities o black tea [].

Te antitumor activity o Hypsizigus marmoreus, anedible mushroom, was investigated against syngeneic tumor,LLC. H. marmoreus increased the lie span, inhibited theactivity o spontaneous tumor metastasis, and decreased thenumber o metastatic nodules. Tese effects were observedonly afer i.p. administration, but not as much by oral admin-istration, and the data showed increased immune activity by competent cells [].

Among the otherliving organismswith antitumor activity against lung cancer, Ganoderma luncidum (a medicinal un-gus) was the most studied and has been used traditionally or the prevention and treatment o cancers or a longtime in traditional Chinese medicine []. In this review,there were eleven reports describing the species G. lucidum(Ganodermataceae), where eight o them investigated thecombination o G. lucidum extracts with antineoplastic drugs.Tis study showed that an aqueous extract o G. lucidum,called “Ling-Zhi or holy mushroom” in traditional Chi-nese medicine, signicantly increased the lie span o LLC-implanted syngeneic CBL/ mice, when administered i.p.alone or in combination with cytotoxic antitumor drugs(Adriamycin, uorouracil, thioguanine, methotrexate, andcisplatin) or a synthetic immunomodulator (Imexon) [].In another study, the authors suggested that the antitumorand antimetastatic activities o the triterpenoid raction o G. lucidum against LLC-implanted mice may be due to theinhibition o tumor-induced angiogenesis. Te compound

identied as ganoderic acid F was obtained rom the acidicraction o the triterpenoid raction o the ruit bodies o G.lucidum as an active substance that inhibited the angiogenesis[]. Recent data showed that triterpenes o G. lucidum haveantilung cancer activity in vitro and in vivo via enhancemento immunomodulation and induction o cell apoptosis [].In addition, G. tsugae, another well-cultivated species o Gan-oderma, was evaluated against lung cancer cells. Te resultsrevealed that the natural product inhibited the viability o H/. cells (doxorubicin-resistant lung adenocarcinoma)in vitro and in vivo and enhanced the growth-suppressiveeffect o doxorubicin on H/. cells. Tis effect is asso-ciated with the downregulation o the PIK/Akt signaling

pathway. Te authors suggest that G. tsugae may be a useuladjuvant therapeutic agent in the treatment o lung cancer[].

o evaluate the effect o the bee venom on the tumorgrowth and metastasis ormation, a transplantable mammary carcinoma (MCA) was used in the syngeneic CBA mouse.

Te results showed that the bee venom suppressed thetumor growth and prolonged the survival o the animalscompared to the controls, afer s.c. or i.v. administration.However, the antimetastatic activity was observed only aferi.v. administration, indicating that the antitumor effect o the bee venom could be highly dependent on the route o injection [].

Consideringall the countries covered in the present study,China, Japan, South Korea, and Ethiopia were those thatpublished the most studies o species with antitumor activity against lung cancer: ten works rom China, eight worksrom Japan, and our publications rom South Korea andEthiopia each. Te most used cell model or the investigationo antitumor activity against lung cancer was LLC. O the studies that showed this cell line as the experimental modelused, showed its sensitivity to the samples tested. Tosedata indicated that this cell line is the most used modelworldwide to evaluate the antitumor activity in lung cancercells. Other models cited in ew studies included NSCLC andadenomas.

3. Conclusions

Several countries have studied medicinal plants with anti-tumor potential, including against lung cancer. Becausemany species are active in different experimental models,the natural products rom plants continue to be a richsource o herbal medicines or biologically active compounds.Tere is a need or urther studies on the standardizationor chemical characterization o the extracts used. Withrespect to pharmacological studies, most o them wereperormed in mice. However, there were also studies withhumans or various species o plants. Tis review showsthat many medicinal herbs have been examined or antilungcancer activity, presenting important results that provideinsight into their use or the treatment o cancer. However,despite many studies showing the evaluation o possiblemechanisms o action o these compounds, the majority o studies still presented only preliminary screening data

and thereore did not describe any mechanism o action.For these studies, they are classied only as “active.” Inaddition, new research ndings have shown extracts aspotential phytotherapeutic adjuvants in advanced lung can-cer therapy. Tis could lead to greater saety and benetsor people, contributing to a better access to health careand thereby a better quality o lie o patients with lungcancer.

Conflict of Interests

Te authors declare no conict o interests.


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Acknowledgments

Te authors thank the University o Illinois at Chicago,USA, or the use o the NAPRALER database or thisstudy and A. Leyva or the English revision o the paper.Tanks are in order also or the nancial support providedby CAPES/CNPq/PRONEX-FAPESQ.

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