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[Special Report]
Anti-cancer properties of Fruits & Vegetables

Ankur Chandra, MD

Introduction

For several decades, diets rich in fruits and vegetables have been correlated with lower rates of malignancies affecting several organ systems.1,2 These phytonutrients, including plant-based phenols, flavonoids, isoflavones, and terpenes among others, have been shown to possess the ability to inhibit the development of carcinogens from precursors, stop the activation of carcinogens, as well as inhibit the neoplasia of cells which have been transformed by these carcinogens to malignancies.3

In present day society, with more commitments and less time, most people do not consume the recommended amount of these substances in the form of a healthy, balanced diet. This review is intended to provide a summary of the current evidence that exists relating these phytonutrients to their anti-tumorigenic properties.

An overview of the phytonutrient packed "Green Drink", NewGreens™ serves as the basis of this review. Five of the seven proprietary blends in NewGreens™ are discussed. FDA Disclaimer: NewGreens™ is not intended to diagnose, treat, cure or prevent any disease.

    Essentia Blend®

Key active ingredients: Alfalfa, Barley grass, Wheat grass, Spirulina

A considerable amount of evidence exists that plant and grass extracts possess potent anti-proliferative effects on several types of malignant cell types. Coumestans, the active phytoestrogen found in alfalfa and clover extracts, has been shown to have beneficial effects in reducing the incidence of breast, colon, and prostate cancer.4 Lunasin, a peptide component of barley grass, has been shown in basic science studies to inhibit neoplastic transformation of fibroblast cells which lead to the development of skin cancer in mouse models.5 The sulfated polysaccharide Spirulina has been shown to inhibit the lung metastases in cases of malignant melanoma by preventing the invasion of these cells through the basement membrane.6 Wheat grass extract has also been shown to prevent chemically-induced colon cancer in laboratory mice.7

    Power Veggie Blend®

Key active ingredients: Carrot, Spinach, Parsley, Broccoli,
Cauliflower, Brussel sprouts

The active compounds in several vegetables have proven in studies to inhibit the development and growth of a variety of malignancies. Carrots, spinach, and parsley have been found to contain a high quantity of major glycolipids with sulfoquinovosyl diacylglycerol (SQDG) being the most active. This SQDG was shown to inhibit DNA polymerase activity (enzyme required for DNA synthesis) and subsequently prevent proliferation of human cancer cells.8 Several members of the Brassica genus, including broccoli, cauliflower, and brussel sprouts, have been found to contain a natural autolytic product known as 3,3'-diindolylmethane (DIM). This DIM has been shown in studies to inhibit Interferon-gamma and subsequently protect against the development of breast cancer in animal models.9

    Antioxidant Supreme Blend®

Key active ingredients: Blueberry, Cherry, Cranberry,
Green Tea, Quercetin

Antioxidants have been studied for decades for their ability to prevent myriad acute and chronic medical conditions from cardiovascular disease to cancer. Several recent studies have shown that the antioxidant properties of various fruits have substantial anti-tumor effects. Polyphenols from blueberry extract has been shown to inhibit the growth of human HT-29 and Caco-2 colon cancer cells while also stimulating the death of these cells.10 Anthocyanins from cherry extracts inhibited the development of colon tumors in genetically modified mice while inhibiting the growth of human colon cancer cells.11 The flavonoid fraction of cranberries has been studied and found to inhibit the growth of several human tumor cell types including colon, skin, breast, prostate, lung, and brain.12 Green tea, and its active compound epigallocatechin-3-gallate (EGCG), has been reported to promote death of chronic lymphocytic leukemia B cells. EGCG is also currently undergoing Phase III clinical trials for the prevention of prostate cancer.13 The bioflavonoid, quercetin glucuronide, is well known to induce growth inhibition in a variety of human cancer cells. In particular, this quercetin proved to both inhibit growth and induce cell death in human lung cancer cells.14

    Gentle Fiber Blend®

Key active ingredients: Flaxseed meal, Apple fiber pectin,
Brown rice bran, Plantago ovata, Glucomannan

Recent interest has been focused on the association of increased dietary fiber and reduced risk of gastrointestinal malignancies, especially colon cancer. Flaxseed meal ingestion has been shown to reduce the incidence of cellular atypia and lesions which may lead to colon cancer in animal models. This has led researchers to suggest that flaxseed meal may play a role in the prevention of colon carcinogenesis.15 Apple fiber pectin, in addition to its bacteriostatic action in altering the intestinal flora, has been associated with decreased colon tumor formation in animal models and decreased metastases to the liver in animals with these lesions.16

Continuing with their protective effects against colon cancer, diets supplemented with brown rice bran have inhibited the development of chemically-induced colon lesion in animal models.17 In cases of inflammatory bowel disease, which in certain cases carry an increased risk of malignancy due to the chronic inflammation in the colonocytes, Plantago ovata has shown to decrease this inflammation by down regulating TNF-alpha and nitric oxide production in rats.18 Glucomannan, a yeast polysaccharide, has shown inhibitory effects against both human lung and fibrosarcoma cell lines.19

    Restorative Detox Blend®

Key active ingredients: Reservatrol, Milk thistle,
Curcumin, Bilberry, Ginger

Of the multitude of phytonutrients which provide antioxidant and regenerative properties, several of these also play a role in the prevention and modulation of cancer. Reservatrol, a natural compound derived from grapes, has demonstrated efficacy in experimental assays examining the inhibition of tumor initiation, promotion, and progression.20 The flavonolignan compounds from milk thistle possess anti-cancer properties against human prostate cancer both in vivo as well as in vitro.21

A multitude of studies have shown that curcumin is effective in both the treatment and prevention of several types of cancer including squamous cell carcinoma, hepatic cancer, lymphoma, lung cancer, and colon cancer. Aggarwal et al. from the MD Anderson Cancer Center reported that the treatment of human head and neck squamous cell carcinoma (HNSCC) cells with curcumin resulted in the inhibition of both growth and survival.22 Notarbartolo et al. from Italy have shown that curcumin treatment of human hepatic cancer cell lines resulted in growth inhibition and promotion of apoptosis.23 In human A549 non-small cell lung cancer cells, curcumin has been shown to increase sensitivity to IFN-Gamma chemotherapy which, without curcumin, was relatively insensitive to this particular cancer type.24

Zhao et al. showed that the anthocyanin extracts from bilberry possesses the ability to inhibit growth of human colon cancer cells.25 Beta-elemene, an extract of the ginger plant, has shown novel anti-cancer effects in human non-small cell lung cancer cells by inducing cell death and inducing a cell cycle arrest, thereby inhibiting proliferation.26

    Conclusion

Given the large and continuously growing body of clinical and scientific evidence, phytonutrients will have an increasing role in the medical management of malignancies of many organ systems. With current lifestyles and diets, many individuals do not ingest these compounds in quantites that will impart these effects. The cooperation of research groups and phytonutrient development and administration will undoubtedly lead to the optimal application of these powerful natural products for the preservation and improvement of our lives.

Written with exclusive rights for Pure Prescriptions, Inc.

    References
1) Beecher GR. Phytonutrients' role in metabolism: effects on resistance to degenerative processes. Nutr. Rev.; 57: S1­6, 1999.
2) Steinmetz KA, Potter JD. Vegetables, fruit and cancer prevention: a review. J Am Diet Assoc; 96: 1027­39, 1996.
3) Rhodes MJC. Physiologically-active compounds in plant foods: an overview. Proc Nutr Soc ; 55: 371­84, 1996.
4) Branca F, Lorenzetti S. Health effects of phytoestrogens. Forum Nutr.; (57): 100-11, 2005.
5) Hyung, J.J. et al. Barley Lunasin Suppresses ras-Induced Colony Formation and Inhibits Core Histone Acetylation in Mammalian Cells.  J. Agric. Food Chem., 50, 5903-5908, 2002.
6) Mishima, T. et al. Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis. Clin. Exp. Metastasis; 16: 541­550, 1998.
7) Zalatnai, A. et al. Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats. Carcinogenesis.; 22(10): 1649-52, 2001.
8) Kuriyamaa, I. et al. Inhibitory effects of glycolipids fraction from spinach on mammalian DNA polymerase activity and human cancer cell proliferation.  Journal of Nutritional Biochemistry; 16: 594­ 601, 2005.
9) Riby JE et al.  Activation and Potentiation of Interferon-{gamma} Signaling by 3,3'-Diindolylmethane in MCF-7 Breast Cancer Cells. Mol Pharmacol. 2005 doi:10.1124/mol.105.017053.
10) Yi, W. et al. Phenolic Compounds from Blueberries Can Inhibit Colon Cancer Cell Proliferation and Induce Apoptosis. J. Agric. Food Chem.; 53: 7320-7329, 2005.
11) Kang, S-Y. et al. Tart cherry anthocyanins inhibit tumor development in ApcMin mice and reduce proliferation of human colon cancer cells.  Cancer Letters; 194: 13­19, 2003.
12) Ferguson, PJ et al.  A Flavonoid Fraction from Cranberry Extract Inhibits Proliferation of Human Tumor Cell Lines.  J. Nutr.; 134: 1529­1535, 2004.
13) Sapone, A. et al. Green tea and its isolated constituents in cancer prevention: Letter to the Editor. Mutation Research; 578: 434­435, 2005.
14) Yang, J-H. et al.  Inhibition of Lung Cancer Cell Growth by Quercetin Glucuronides via G2/M Arrest and Induction of Apoptosis. DMD, 2005. doi:10.1124/dmd.105.005280
15) Serraino M, Thompson LU.  Flaxseed supplementation and early markers of colon carcinogenesis. Cancer Lett.; 63(2): 159-65, 1992. 16) Tazawa K. et al. Dietary fiber inhibits the incidence of hepatic metastasis with the anti-oxidant activity and portal scavenging functions. Hum Cell.; 4: 189-96, 1999.
  17) Katyama M. et al. Preventive effect of fermented brown rice and rice bran against colon carcinogenesis in male F344 rats. Oncol Rep.; 9(4): 817-22, 2002.
18) Rodr¦guez-Cabezas, ME et al. Dietary Fiber Down-Regulates Colonic Tumor Necrosis Factor-? and Nitric Oxide Production in Trinitrobenzenesulfonic Acid-Induced Colitic Rats.  J. Nutr.; 132: 3263­3271, 2002.
  19) Kumano, N. et al. Antitumor effect of the yeast polysaccharide preparation in syngeneic mouse tumor models. Tohoku J Exp Med.; 146(1): 89-96, 1985.
20) Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas, C. V.; Beecher, C. W. W. B.; Fong, H. H. S.; Farnsworth, N. R.; Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science; 275: 218-220, 1997.
21) Davis-Searles, PR et al. Milk Thistle and Prostate Cancer: Differential Effects of Pure Flavonolignans from Silybum marianum on Antiproliferative End Points in Human Prostate Carcinoma Cells. Cancer Res; 65(10): 4448-57, 2005.
22) Aggarwal et al.  Inihibition of Growth and Survival of Human Head and Neck Squamous Cell Carcinoma Cells by Curcumin via Modulation of Nuclear Factor-?B Signaling. Int. J. Cancer: 111, 679­692, 2004.
23) Notarbartolo et al.  Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression.  Cancer Lett; 224: 53­65, 2005.
24) J. Lee et al. Curcumin inhibits interferon-a induced NF-jB and COX-2 in human A549 non-small cell lung cancer cells.  Biochemical and Biophysical Research Communications; 334: 313­318, 2005.
25) Zhao, C. et al. Effects of Commercial Anthocyanin-Rich Extracts on ColonicCancer and Nontumorigenic Colonic Cell Growth.  J. Agric. Food Chem.; 52: 6122-6128, 2004.
26) Wang, G. et al.  Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death.  Cell Mol Life Sci.; 62(7-8): 881-93, 2005.

    Further Reading
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