available through online review article ...health care system by a continuous preventive mechanism...

Y. N. Gholse* et al. /International Journal Of Pharmacy&Technology

IJPT | April-2012 | Vol. 4 | Issue No.1 | 1950-1973 950

ISSN: 0975-766X

CODEN: IJPTFI Available through Online Review Article

www.ijptonline.com DEVELOPMENTS IN NUTRACEUTICALS FOR CHEMOPREVENTION: A REVIEW

Y. N. Gholse*, S. R. Yadav J. L. Chaturvedi College of Pharmacy, Electrical zone bldng, MIDC, Hingna road, Nagpur-440016.

Email: [email protected] Received on 22-03-2012 Accepted on 10-04-2012

Abstract

In recent years there is a growing interest in nutraceuticals which provide health benefits and are alternative to

modern medicine. Nutrients, herbals and dietary supplements are major constituents of nutraceuticals which make

them instrumental in maintaining health, act against various disease conditions and thus promote the quality of life.

Epidemiological and clinical studies have demonstrated the relationship between diet and health status. It is well

known that populations consuming a large proportion of plant-based foods, including fruits, vegetables, whole grains

and cereals or those with a high intake of seafoods, have a lower incidence of cardiovascular diseases and certain

types of cancer. Functional foods and nutraceuticals may provide a means to reduce the increasing burden on the

health care system by a continuous preventive mechanism Therefore; interest has been expressed in functional foods,

nutraceuticals and dietary supplements. Functional foods are defined as being similar in appearance to conventional

foods, are consumed as part of a usual diet, and are known to improve health status and render physiological effects

beyond basic nutritional function expected of conventional foods. Chemoprevention is the use of small molecules,

including dietary or herbal chemicals, to prevent diseases, as opposed to chemotherapeutics, where chemicals,

mostly synthetic, are used to remove or alleviate the symptom of diseases. However, nutraceuticals are products

produced from foods, but sold in the medicinal form of capsule, tablet, powder, solution, or potion. They are not

generally associated with food and have demonstrated physiological benefits and/or provide protection against

chronic diseases; these are now referenced as “natural health products”.


IJPT | April-2012 | Vol. 4 | Issue No.1 | 1950-1973 Page 1951

Keywords: Cancer, Chemoprevention, Natural health products, Nutraceuticals.

Introduction: In the past five years, the world has witnessed the explosive growth of a multibillion dollar industry

known as nutraceuticals. The term “nutraceutical” combines the word “nutrient” (a nourishing food or food

component) with “pharmaceutical” (a medical drug)1. Conventional cancer treatment has been in place for over 50

years with little change in the overall strategy. Tumors are removed surgically, while remaining inoperable sites are

treated with radiation, chemotherapy or both. These latter modalities nonspecifically target all tissues, the only

differentiation being their rapidity of growth and the focusing possible with directed radiation and certain methods

of chemotherapy delivery. As a result, collateral damage and adverse side effects are the rule. The severity of these

adverse effects has stimulated a continuing search for ways to reduce them. As the research has progressed, there has

developed a growing consensus that a variety of nutraceuticals can complement the effects of standard cancer

treatment. Their contributions are several2,3 [Fig.1]:

• Nutraceuticals can decrease the side effects of conventional cancer treatment.

• Nutraceuticals can protect normal cells from the indiscriminate damage done by cancer treatment.

• Nutraceuticals can enhance the effects of cancer treatment

• Nutraceuticals can abrogate or delay the onset of cancer

• Nutraceuticals can destroy cancer after it appears.

A single admonition and three specific caveats accompany such recommendations. There is a fear that the

antioxidant supplements that protect normal cells from chemotherapy will also protect cancer cells. Research has

identified only three potential antagonistic interactions among the many nutraceutical and chemotherapeutic agent

combinations studied. [Fig.2] Beyond these three, the results have been universally benign, both in the laboratory

and in clinical trials.

Carotenoids

Recent epidemiologic studies have shown good correlation between dietary intake of tomato and reduced risk of

cancer and cardiovascular diseases4. Tomato is rich in various carotenoids. Lycopene is the precursor of carotene in



tomato, which accumulates after the lycopene cyclase gene is down regulated during ripening5. Lycopene and

carotene can induce apoptosis in prostate cancer cells6 and malignant lymphoblast cells at a concentration range of 3

to 30 M within 24 h. The carotenoid-induced apoptosis shows typical DNA fragmentation, poly ADP-ribose

polymerase (PARP) cleavage, and caspase-3 activation7. However, in the case of insulin-like growth factor-1–

stimulated growth of MCF-7 mammary cancer cells, the inhibitory effect of lycopene may be independent of

apoptosis8. Although it is certain that carotenoids have antiproliferative activity, it is unclear what the direct

molecular targets of lycopene and carotene. Carotene has been shown to affect NF-_B binding activity9, whereas

lycopene causes an increase in connexin-43 mRNA and stimulates gap junction communication at a concentration

(0.1 M) much lower than that required for apoptosis10. Thus, it is likely that the biological effects of carotenoids are

pleiotropic, and their chemopreventive activity may not be solely due to apoptosis.

Antioxidants

Antioxidants protect the body from destructive free radicals, which are generated when the body uses oxygen to

make energy and from exposure to environmental factors, such as cigarette smoke. Left unchecked, free radicals

cause uncontrollable chemical reactions that damage the body11. Radiotherapy and some forms of chemotherapy

function by creating oxidizing free radicals that damage malignant cells. The chemotherapeutic agents most noted

for creating cellular damage by generating free radical oxidants are the alkylating agents (e.g., cyclophospamide,

ifosamide), the tumor antibiotics (e.g., doxorubicin, bleomycin), and the "platinum" compounds (e.g., cisplatin).

Since antioxidants are free-radical scavengers, their use in combination with these agents must be explored before

being recommended. Sufficient evidence from research has justified the practice, although the mechanism by which

these nutraceuticals exert opposite effects on normal and malignant cells has yet to be fully elucidated. Two theories

have been proposed, both of which require an exploration of the mechanisms of action of cancer treatments12.

Traditionally it has been thought that DNA damage leading to cell necrosis is the way radiation and chemotherapy

kill cancers.[Fig.3] More recently evidence suggests, however, that damage of a lesser severity, perhaps to cell

membranes by lipid peroxidation, arrests mitosis and initiates apoptosis13. Since many antioxidant treatments



stimulate apoptotic pathways, such an effect might override any potential antagonism14,15. This effect is likely to be

further enhanced by an intrinsic deficit in malignant cell repair mechanisms. A dramatic deficiency of catalase has

been identified in many cancers.

When cells with this deficiency are treated with vitamin C, hydrogen peroxide accumulates, and the cells die.

Adding catalase to these cell cultures completely nullifies the effect16,17. In the laboratory, cancer cell cultures have

demonstrated a variety of beneficial results from the addition of a mixture of antioxidants. Numerous tumor growth

inhibitory signals have been generated, among them inhibited expression the activity of protein kinase C and

increased expression of transforming growth factor (TGF) mRNA, TGF protein and its secretion, and the expression

of p21 and wild-type p53. Specific nutraceuticals have by themselves generated many other beneficial effects,

although the results have not been entirely benign. Certain individual antioxidants at low doses have been shown to

stimulate the growth of some cancers. Others, given individually even at high doses, have had no effects whatsoever.

And the effects of many agents at both low and high doses have yet to be defined. Therefore, carefully designed

regimens, usually involving multiple agents at tested dosages, have been advocated, rather than individual

supplements used alone or indiscriminate combinations in poorly controlled doses18. One clinical study compared

standard paclitaxel and carboplatin chemotherapy for non-small-cell lung cancer with and without ascorbic acid

6100 mg/day, dl-alpha-tocopherol (vitamin E) 1050 mg/day and beta-carotene 60 mg/day. A tendency to favor the

combined regimen appeared but was statistically insignificant at p = 0.2019. Most of the research that has evaluated

the effects of antioxidants on cancer has been conducted in a laboratory and because of this it is considered

experimental. But it nonetheless serves important roles in the research process: It helps determine the activity of a

compound and directs future clinical trials.

Flavonoids

Flavonoids are plant compounds known to have antioxidant properties in vitro and in vivo. Flavonoids are a group of

more than 4000 polyphenolic compounds that occur naturally in foods of plant origin. These compounds possess a

common phenylbenzopyrone structure (C6-C3- C6), and they are categorized according to the saturation level and



opening of the central pyran ring, mainly into flavones, flavonols, isoflavones, flavonols, flavanone, and

flavanonols20. Many of the thousands of flavonoids in nature have been studied for anticancer properties. The most

well characterized anti-tumor flavonoids are epigallocatechin gallate (from green tea), genistein (from soy and red

clover), curcumin (from turmeric), silibinin (from milk thistle). Among them, tea polyphenols, quercetin, and

genistein have been widely studied for their potential chemopreventive applications. Although epidemiologic studies

have not yielded a clear positive correlation between tea consumption and cancer risk reduction, there is no doubt

that tea extracts or tea polyphenols have promising anticancer effects in animal models 21,22. In addition to cancer,

tea polyphenols may have protective effect for cardiovascular and inflammatory diseases23. Epigallocatechin gallate

(EGCG; Figure 2B) and other catechins were first shown to be apoptotic in human lymphoid leukemic cells24 and

human carcinoma cells25. Similar observation has since been extended to lung tumor cell lines26, colon cancer cells,

breast cancer cells and virally transformed human fibroblasts27, prostate cancer cells28, stomach cancer cells29, brain

tumor cells30, head and neck squamous carcinoma31, and cervical cancer cells.32 The effective dosages of EGCG for

apoptosis in these cells are in the range of 20 to 100 µM, and the time course varies from 10 to 30 h. Based on the

study of using p53-dominant negative mutant or p53 knockout cells, it is thought that intrinsic and extrinsic

apoptotic pathways are involved in the action of EGCG.33-35.

Maitake Mushrooms

Amazing cancer cure case studies with maitake mushroom has been clinically proven to prevent and heal cancer, as

well as decrease and even eliminate cancerous tumors. Maitake (grifola frondosa) is a polypore mushroom that is

native to Japan. It grows in clusters at the base of trees, particularly oaks, and has been prized for its medicinal

properties for centuries. It is commonly known as Hen of the Woods, Ram’s Head and Sheep’s Head, and its

Japanese name, maitake, literally means “dancing mushroom,” a term derived from Japanese folk medicine.[Fig.4]

Maitake is best known for its cancer-fighting properties. In 2009, a phase I/II human trial was conducted by

Memorial Sloan-Kettering Cancer Center, and it showed that maitake extract stimulates the immune systems of

breast cancer patients. A particular mushroom native to Japan has generated substantial interest for its ability to



inhibit tumor growth. Maitake (Grifola frondosa) is so rare and so delicious that folks dance when they find it, hence

the literal translation "dancing mushroom." It was singled out after 15 years of mushroom research by one

investigator using MM46 mice with breast cancer.

Mice receiving either oral or intraperitoneal Maitake extract had either complete or >75% remission of their tumors

36. Powders and extracts of this mushroom, identified as Maitake D-fraction (Maitake Products, Inc.) and Maitake

crude powder, have produced remarkable improvements in advanced breast, lung and liver cancers and some

suggested benefits in leukemia, stomach and brain cancer patients. It appears to increase immune cell activity,

generating increases in TNF-alpha and IFN-gamma from spleen cells and TNF alpha expressed in NK cells. It also

increases macrophagederived interleukin-12, which serves to activate NK cells37-40. In the laboratory, D-fraction, a

heta-glucan, was tested in combination with carmustine (BCNU), 5-fluorouracil (5-FU), methotrexate (MTX),

etoposide, cisplatin and mitomycin C on prostate cancer cell cultures. BCNU, 5-FU and MTX produced a 50%

reduction in cell viability. Only the combination of BCNU and D-fraction increased the death rate to -90%. The

increased death rate was accompanied by -80% reduction in the activity of glutathione-dependent detoxifying

enzyme glyoxalase-I, suggesting a mechanism for the observed effect41. Other laboratory studies involving Maitake

D-Fraction (MDF), a standardized form of maitake mushroom containing grifolan — an important beta-glucan

polysaccharide, show evidence of MDF’s therapeutic value. It exhibits anti-cancer activity, has the ability to block

the growth of cancer tumors and boost the immune function of mice with cancer.

Stilbenes

The distribution of stilbenes in the plant kingdom is wide. Resveratrol, for example, is found in small fruits such as

grapes and Vaccinium berries, peanuts and in Polygonum species. Stilbenes structurally related to resveratrol have

been found in a variety of foods as well as in medicinal plants Similar to resveratrol, these phytochemicals have a

multitude of biological activities [Fig. 5]. Resveratrol (3,5,4-trihydroxy-trans-stilbene;), a phytoalexin present in

grapes, peanuts, and pines, has antioxidant and anti-inflammatory activities42 and is the active ingredient in

Leguminoseae that inhibits cellular events associated with tumor initiation, promotion, and progression in a mouse



skin cancer model43. In vitro mechanisms of action of the most representative stilbene, resveratrol, have been

extensively discussed in numerous reports and reviews . Its potential as a cancer chemopreventive agent has been

extensively reviewed recently44-47. The possible role of resveratrol, a phytoestrogen, in cardiovascular protection

has been reviewed recently48-49. Resveratrol and other related stilbenes suppress the proliferation of awide variety of

cultured cancer cells, including colon, prostate, breast, pancreas, ovary, melanoma, head and neck, and others . In

vitro, resveratrol induces apoptosis and inhibits the growth of various human tumor cells, including oral squamous

carcinoma50, promyelocytic leukemia51, human breast cancer cells52, prostate cancer cells53,54, esophageal carcinoma

cells55, pancreatic cancer cells56, and monocytic leukemia cells57. Several key mechanisms of action include

inhibition of the transcription factor NF-κB , regulation of cytochrome P450 enzymes , activation of nuclear

receptors such as estrogen receptors (ERs) , and peroxisome proliferator-activated receptors (PPARs) , inhibition of

expression and activity of inflammation-related enzymes such as cyclooxygenases , and regulation of sirtuins. The

dosage of resveratrol used in various studies has varied between 10 and 300 µM, with apoptosis appearing between

24 and 96 h. Induction of p53 at the mRNA and protein levels is the most commonly observed effect of resveratrol

and is considered the major cause for apoptosis. We found that resveratrol does not exhibit a clear differential

growth inhibitory effect toward transformed human fibroblasts. Interestingly, a resveratrol analog, 3,4,5,4-

tetrahydroxystilbene, is more potent than resveratrol in inducing apoptosis of transformed cells, but has no effect on

normal counterparts at much higher concentrations58.

Proteolytic Enzymes

Proteolytic enzymes (or proteases) refer to the various enzymes that digest (break down into smaller units) protein.

These enzymes include the pancreatic proteases chymotrypsin and trypsin, bromelain (pineapple enzyme), papain

(papaya enzyme), fungal proteases, and Serratia peptidase (the “silk worm” enzyme).Among the proteolytic

enzymes of interest to oncology, trypsin and chymotrypsin from cattle or pigs, papain from papaya sap, and

bromelain from pineapple stems are the most studied .



Bromelain contains nine active proteases. They reduce the adverse effects caused by radiotherapy and chemotherapy

and, prolong survival. One study of patients with inoperable lung cancer treated with fluorouracil, vinblastine,

methotrexate and cyclophosphamide found a reduction in leukopenia, mucusitis and uremia in patients who received

in addition a combination of papain, trypsin and chymotrypsin. The mean survival also increased by 25%. The same

combination reduced the elevation in liver enzymes caused by carboplatin, epiruhicin and prednimustine treatment

of ovarian carcinoma59 and prolonged survival by 76% in patients treated with a variety of regimens for multiple

myeloma60 [Table 1]. Several studies augmenting radiotherapy with the same combination of proteolytic enzymes

produced improvements in radiation side effects or disease progress [Table 2]. The effects of proteolytic enzymes

are not well understood as yet, but they appear to be based on induction of antiproteinases and on alterations of

cytokine composition inducing anti-inflammatory effects61 . Among patients who have pancreatic cancer, those who

chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better

quality of life than those who chose proteolytic enzyme treatment.

Curcumin

Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called ‘‘curry powder”) that has

been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E),

apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR,

and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF),

metastasis (CXCR-4) and inflammation (NF-jB, TNF, IL-6, IL-1, COX-2, and 5-LOX).[Fig.6] The activity of

curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer,

ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma

reflects its ability to affect multiple targets. Thus an ‘‘old-age” disease such as cancer requires an ‘‘age-old”

treatment62. Curcumin (diferuloylmethane), a polyphenol derived from the turmeric plant, is a potent antioxidant and

anti-inflammatory agent. During 50 years of research it has shown an ability to suppress initiation, proliferation and

metastasis of a wide variety of tumor cell lines. Its many mechanisms of action include down-regulating the



expression of C0X2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules, cyclin DI and

growth factor receptors (such as EGFR and HER2). It also inhibits the activity of c-Jun N-terminal kinase, protein

tyrosine kinases and protein serine/threonine kinases.[Fig.7]

Even at high doses it has demonstrated no dose-limiting toxicity and thus offers considerable promise as a cancer

treatment, although human cancer studies should be completed and published to further validate its effects and

initiate widespread implementation of this cancer treatment strategy63. Extensive research for decades has made the

clear conclusion that curcumin appears beneficial therapeutic effects on inflammation-related diseases including

cancer. Marked by chronic inflammation modulator, NF-κB is the major molecular target of curcumin treatments.

Since blocking of I-κB degradation and its control by IKK are essential steps in down-regulating NF-κB activation,

targeting this point by curcumin for NF-κB-specific blockage without safety concern is worth exploring in future64.

Quercetin

Quercetin is a flavonoid molecule ubiquitous in nature. A number of its actions make it a potential anti-cancer agent,

including cell cycle regulation, interaction with type II estrogen binding sites, and tyrosine kinase inhibition.

Quercetin appears to be associated with little toxicity when administered orally or intravenously65. Quercetin, a

flavonoid antioxidant present in many yellow vegetables, has been studied extensively in the laboratory and

occasionally in human cancer trials. It is able to alter the concentration of chemotherapeutic agents inside cancer

cells, affect cell cycle regulation, interact with type II estrogen binding sites, and inhibit tyrosine kinase, frequently,

but not always, generating an anticancer effect 66,67 [Fig.8]. It is also able to overcome anti-apoptotic mutations that

result in drug resistance in human tumors.[Fig.9] It is proposed that quercetin could be used in both the prevention

and treatment of cancer and that diet would likely fulfill the concentration requirements for prevention, but

supplementation or another form of delivery could be necessary for therapeutic responses. Enzymatic modification

of quercetin could further lower the threshold necessary for anti-tumor activity 68.



Graviola (Annona Muricata)

Many bioactive compounds and phytochemicals have been found in graviola, as scientists have been studying its

properties since the 1940s. Its many uses in natural medicine have been validated by scientific research. Several

studies by different researchers demonstrated that the bark as well as the leaves had hypotensive, antispasmodic,

anticonvulsant, vasodilator, smoothmuscle relaxant, and cardiodepressant activities in animals69,70. The leaves, bark,

and stems of Graviola, an evergreen indigenous to tropical areas in South and North America including the Amazon,

show remarkable cytotoxicity and selectivity against cancer cells. The phytochemical group, Annonaceous

acetogenins, seems to play a significant role in this tree's antitumor properties71-74 [Fig.10]. In 1976 plant screening

program by the National Cancer Institute, graviola leaves and stem showed active cytotoxicity against cancer cells

and researchers have been following up on these findings since75. Much of the cancer research on graviola focuses

on a novel set of phytochemicals called Annonaceous acetogenins. Graviola produces these natural compounds in its

leaf and stem, bark, and fruit seeds. Three separate research groups have isolated these acetogenin compounds in

graviola which have demonstrated significant antitumorous and anticancerous properties, and selective toxicity

against various types of cancer cells (without harming healthy cells) publishing eight clinical studies on their

findings76-83. Many of the acetogenins have demonstrated selective toxicity to tumor cells at very low dosages—as

little as 1 part per million. Four studies were published in 1998 which further specify phytochemicals and

acetogenins which are demonstrating the strongest anticancerous, antitumorous, and antiviral properties84-87. Thus

far, specific acetogenins in graviola have been reported to be selectively toxic to these types of tumor cells: lung

carcinoma cell lines; human breast solid tumor lines; prostate adenocarcinoma; pancreatic carcinoma cell lines;

colon adenocarcinoma cell lines; liver cancer cell lines;88,89, human lymphoma cell lines;90 and multi-drug resistant

human breast adenocarcinoma91.

The group of compounds found in Graviola are potent inhibitors of NADH: ubiquinone oxidoreductase, which is an

essential enzyme in complex I leading to oxidative phosphorylation in mitochondria. They also inhibit the

ubiquinone-linked NADH oxidase enzyme, which is specific to the plasma membranes of cancerous cells. Much of



the recent research done on extracts of this tree has been conducted by Purdue University, supported by grants from

the National Cancer Institute and the National Institutes of Health . What they have found is that Annonaceous

acetogenins can selectively inhibit the growth of cancerous cells and also inhibit the growth of adriamycin and other

drug-resistant tumor cells. Not only are the compounds effective in killing tumors that have proven resistant to anti-

cancer agents, but they also have a special affinity for such resistant cells. And we know the mechanism of action of

at least one compound in ihe Annonaceous acetogenin group, bullatacin, which preferentially kills multi-drug

resistant cancer cells by inhibiting ATP production, and thus removing the cancer's energy source.

Conclusion

Nutraceuticals are destined to play an important role in future therapeutic developments but their success will be

governed by control of purity, safety and efficacy without inhibiting innovation. Nutraceuticals will continue to

appeal because they are convenient for today’s lifestyle. Over 50 years of research has shown that cancer is easier to

prevent than cure. Whether preventing cancer or treating it once it has occurred, it is clear that this disease is

multifactorial and that treatment necessitates the modulation of multiple pathways and targets. The targeted actions

of chemopreventive nutraceutical agents, such as those present in fruits and vegetables, are increasingly being

recognized as useful in the therapy of cancer. Among the targets subject to modulation by these agents are activation

of apoptosis; suppression of growth factor expression or signaling; down regulation of antiapoptotic proteins; and

downregulation of angiogenesis through inhibition of vascular endothelial growth factor expression,

cyclooxygenase-2, matrix metalloproteinase-9, urokinase-type plasminogen activator and adhesion molecules.

Furthermore, phytochemicals can modulate these molecular targets with considerably greater safety than standard

radiation and chemotherapeutic agents. This article has covered some of these chemicals but there are more.

Genistein, resveratrol, dially sulfide, isothiocyanates, S-aiiy cysteine, allicin, lycopene, capsaicin, 6-gingerol, ellagic

acid, ursolic acid, betulinic acid, flavopiridol, silymarin, anethol, catechins and eugenol, are among the many

naturally occurring agents being studied for use in cancer treatment. Recent work has shown that these and other

phytochemicals work synergistically with chemotherapy regimens and can reverse chemoresistance. Because of their



pharmacological safety, select antioxidants, Maitake mushrooms, fruits, vegetables, curcumin, quereetin, Graviola,

and other well-researched phytochemical agents can be used alone or in combination with standard chemotherapy to

treat cancer, and alone, to prevent its onset. Chemopreventive agents are much sought after as an early interventional

approach to prevent tumor development or to lower the incidence risk of cancers. Given that the current available

methods of treatment are chemotherapy, radiation, and surgery, all of which can induce significant side effects, an

urgent need for alternate or adjuvant therapies has arisen. Phytochemicals are relatively safe and abundantly

available from dietary sources. Therefore, alternate medicine aims at harnessing the protective properties of these

nonessential nutrients toward cancer prevention and treatment.

TABLES:

Table-1: Clinical Studies of Proteolytic enzymes patients receiving chemotherapy

Table-2: Clinical Studies of Proteolytic enzymes in patients receiving radiation therapy



FIGURES:

Fig. 1. Nutraceuticals: Safety and Efficacy

Fig. 2. Pathway influenced by Nutraceutical



Fig. 3. Role of antioxidants in cancer treatment

Fig. 4. Maitake Mushrooms(Grifola frondosa)

Fig. 5. Naturally-occurring stilbenes



Fig. 6. Role of Curcumin in cancer treatment

Fig. 7. Role of Curcumin in cancer treatment



Fig.8 . Role of Quercetin in cancer treatment

Fig. 9. Role of Quercetin in cancer treatment



Fig.10. Graviola (Annona Muricata)

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Corresponding Author:

Y. N. Gholse*, S. R. Yadav

Email: [email protected]

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