The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention.

Green tea (Camellia sinensis) is rich in catechins, of which (-)-epigallocatechin-3-gallate (EGCG) is the most abundant. Studies in animal models of carcinogenesis have shown that green tea and EGCG can inhibit tumorigenesis during the initiation, promotion and progression stages. Many potential mechanisms have been proposed including both antioxidant and pro-oxidant effects, but questions remain regarding the relevance of these mechanisms to cancer prevention. In the present review, we will discuss the redox chemistry of the tea catechins and the current literature on the antioxidant and pro-oxidative effects of the green tea polyphenols as they relate to cancer prevention. We report that although the catechins are chemical antioxidants which can quench free radical species and chelate transition metals, there is evidence that some of the effects of these compounds may be related to induction of oxidative stress. Such pro-oxidant effects appear to be responsible for the induction of apoptosis in tumor cells. These pro-oxidant effects may also induce endogenous antioxidant systems in normal tissues that offer protection against carcinogenic insult. This review is meant point out understudied areas and stimulate research on the topic with the hope that insights into the mechanisms of cancer preventive activity of tea polyphenols will result.

[1]  S. Aust,et al.  The role of iron in the initiation of lipid peroxidation. , 1987, Chemistry and physics of lipids.

[2]  Sara Khan,et al.  Studies on the protective effect of green tea against cisplatin induced nephrotoxicity. , 2009, Pharmacological research.

[3]  V. L. Singleton,et al.  Phenolic Browning: A Perspective from Grape and Wine Research , 1995 .

[4]  K. Fukuzawa,et al.  Site-specific induction of lipid peroxidation by iron in charged micelles. , 1988, Archives of biochemistry and biophysics.

[5]  S. Wiseman,et al.  The chemistry of tea flavonoids. , 1997, Critical reviews in food science and nutrition.

[6]  S. Eksborg,et al.  Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostine cannot protect against this cytotoxicity. , 2005, Cancer research.

[7]  G. Mazzanti,et al.  Hepatotoxicity from green tea: a review of the literature and two unpublished cases , 2009, European Journal of Clinical Pharmacology.

[8]  S. Sang,et al.  Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  S. Wiseman,et al.  Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. , 2003, The Journal of nutrition.

[10]  R. Prior,et al.  Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. , 2005, Journal of agricultural and food chemistry.

[11]  Giovanni Castagnetti,et al.  Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. , 2006, Cancer research.

[12]  A. Davison,et al.  Reaction of oxygen with 6-hydroxydopamine catalyzed by Cu, Fe, Mn, and V complexes: identification of a thermodynamic window for effective metal catalysis. , 2001, Archives of biochemistry and biophysics.

[13]  Chung S. Yang,et al.  DOSE-DEPENDENT LEVELS OF EPIGALLOCATECHIN-3-GALLATE IN HUMAN COLON CANCER CELLS AND MOUSE PLASMA AND TISSUES , 2006, Drug Metabolism and Disposition.

[14]  L. Sherwood Human Physiology : From Cells to Systems , 1989 .

[15]  K. Yodogawa,et al.  Tea catechin consumption reduces circulating oxidized low-density lipoprotein. , 2007, International heart journal.

[16]  H. Tachibana Molecular basis for cancer chemoprevention by green tea polyphenol EGCG. , 2009, Forum of nutrition.

[17]  A. Davison,et al.  6-hydroxydopamine does not reduce molecular oxygen directly, but requires a coreductant. , 1984, Archives of biochemistry and biophysics.

[18]  Joan-Hwa Yang,et al.  Supplementary catechins attenuate cooking-oil-fumes-induced oxidative stress in rat lung. , 2009, The Chinese journal of physiology.

[19]  Kuo-Chin Huang,et al.  Chronic green tea extract supplementation reduces hemodialysis-enhanced production of hydrogen peroxide and hypochlorous acid, atherosclerotic factors, and proinflammatory cytokines. , 2007, The American journal of clinical nutrition.

[20]  Chi-Tang Ho,et al.  ANTIOXIDANT CHEMISTRY OF GREEN TEA CATECHINS: OXIDATION PRODUCTS OF (-)-EPIGALLOCATECHIN GALLATE AND (-)-EPIGALLOCATECHIN WITH PEROXIDASE , 2007 .

[21]  Sandra N. Mohr,et al.  Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[22]  D. Alberts,et al.  Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[23]  G. DiLabio,et al.  Predicting the activity of phenolic antioxidants: theoretical method, analysis of substituent effects, and application to major families of antioxidants. , 2001, Journal of the American Chemical Society.

[24]  A. I. Dorozhko,et al.  Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. , 1989, Biochemical pharmacology.

[25]  A. Davison,et al.  Interactions between metals, ligands, and oxygen in the autoxidation of 6-hydroxydopamine: mechanisms by which metal chelation enhances inhibition by superoxide dismutase. , 1987, Archives of biochemistry and biophysics.

[26]  D. Alberts,et al.  Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[27]  Chi-Tang Ho,et al.  Synthesis and structure identification of thiol conjugates of (-)-epigallocatechin gallate and their urinary levels in mice. , 2005, Chemical research in toxicology.

[28]  J. Abian,et al.  Complexes of iron with phenolic compounds from soybean nodules and other legume tissues: prooxidant and antioxidant properties. , 1997, Free radical biology & medicine.

[29]  H. Bonkovsky Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). , 2006, Annals of internal medicine.

[30]  Xiaofeng Meng,et al.  Stability, cellular uptake, biotransformation, and efflux of tea polyphenol (-)-epigallocatechin-3-gallate in HT-29 human colon adenocarcinoma cells. , 2002, Cancer research.

[31]  T. Stevens,et al.  Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. , 2005, Annals of internal medicine.

[32]  M. Jimenez-saenz,et al.  Acute hepatitis associated with the use of green tea infusions. , 2006, Journal of hepatology.

[33]  Rui M. Rocha,et al.  Interactions of Flavonoids with Iron and Copper Ions: A Mechanism for their Antioxidant Activity , 2002, Free radical research.

[34]  M. S. Butt,et al.  Green Tea: Nature's Defense against Malignancies , 2009, Critical reviews in food science and nutrition.

[35]  G. Yang,et al.  Effect of black and green tea polyphenols on c-jun phosphorylation and H(2)O(2) production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction. , 2000, Carcinogenesis.

[36]  Anton Rietveld,et al.  Antioxidant effects of tea: evidence from human clinical trials. , 2003, The Journal of nutrition.

[37]  Di Chen,et al.  Green tea and tea polyphenols in cancer prevention. , 2004, Frontiers in bioscience : a journal and virtual library.

[38]  P. Maliakal,et al.  Tea consumption modulates hepatic drug metabolizing enzymes in Wistar rats , 2001, The Journal of pharmacy and pharmacology.

[39]  P. O'Brien,et al.  Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. , 2006, Free radical biology & medicine.

[40]  Jen-kun Lin,et al.  Suppression of extracellular signals and cell proliferation through EGF receptor binding by (−)‐epigallocatechin gallate in human A431 epidermoid carcinoma cells , 1997, Journal of cellular biochemistry.

[41]  V. L. Singleton,et al.  The Production of Aldehydes as a Result of Oxidation of Polyphenolic Compounds and its Relation to Wine Aging , 1974, American Journal of Enology and Viticulture.

[42]  John C. Danilewicz,et al.  Review of Reaction Mechanisms of Oxygen and Proposed Intermediate Reduction Products in Wine: Central Role of Iron and Copper , 2003, American Journal of Enology and Viticulture.

[43]  H. Nakagawa,et al.  Generation of hydrogen peroxide primarily contributes to the induction of Fe(II)-dependent apoptosis in Jurkat cells by (-)-epigallocatechin gallate. , 2004, Carcinogenesis.

[44]  V. Adhami,et al.  Antioxidants of the beverage tea in promotion of human health. , 2004, Antioxidants & redox signaling.

[45]  A. Kong,et al.  Comparison of (−)-Epigallocatechin-3-Gallate Elicited Liver and Small Intestine Gene Expression Profiles Between C57BL/6J Mice and C57BL/6J/Nrf2 (−/−) Mice , 2005, Pharmaceutical Research.

[46]  M. Masuda,et al.  Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[47]  A. Gescher,et al.  Breast cancer prevention by green tea catechins and black tea theaflavins in the C3(1) SV40 T,t antigen transgenic mouse model is accompanied by increased apoptosis and a decrease in oxidative DNA adducts. , 2007, Journal of agricultural and food chemistry.

[48]  Mohammad Saleem,et al.  Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. , 2006, Cancer research.

[49]  P. Kalaiselvi,et al.  Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats , 2008, Experimental Gerontology.

[50]  B. Halliwell Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? , 2008, Archives of biochemistry and biophysics.

[51]  B. Frei,et al.  Tea Catechins and Polyphenols: Health Effects, Metabolism, and Antioxidant Functions , 2003, Critical reviews in food science and nutrition.

[52]  S. Cox,et al.  Modulation of aflatoxin biomarkers in human blood and urine by green tea polyphenols intervention. , 2008, Carcinogenesis.

[53]  Yan Li,et al.  Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats. , 2003, World journal of gastroenterology.

[54]  J. Schwartz,et al.  Molecular and cellular effects of green tea on oral cells of smokers: a pilot study. , 2005, Molecular nutrition & food research.

[55]  A. Furukawa,et al.  Catechins Induce Oxidative Damage to Cellular and Isolated DNA through the Generation of Reactive Oxygen Species , 2003, Free radical research.

[56]  I. Rietjens,et al.  Role of catechin quinones in the induction of EpRE-mediated gene expression. , 2008, Chemical research in toxicology.

[57]  D. Alberts,et al.  Modulation of Human Glutathione S-Transferases by Polyphenon E Intervention , 2007, Cancer Epidemiology Biomarkers & Prevention.

[58]  J. Lambert,et al.  Laboratory, epidemiological, and human intervention studies show that tea (Camellia sinensis) may be useful in the prevention of obesity. , 2010, The Journal of nutrition.

[59]  A. Girotti,et al.  Damaging effects of oxygen radicals on resealed erythrocyte ghosts. , 1984, The Journal of biological chemistry.

[60]  Xin Wang,et al.  Cancer prevention by tea: animal studies, molecular mechanisms and human relevance , 2009, Nature Reviews Cancer.

[61]  P. Maliakal,et al.  Inhibition of carcinogenesis by tea. , 1997, Nature.

[62]  Gang Lu,et al.  Possible mechanisms of the cancer-preventive activities of green tea. , 2006, Molecular nutrition & food research.

[63]  P. Kalaiselvi,et al.  Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (−)-epigallocatechin-3-gallate , 2008, International Journal of Developmental Neuroscience.

[64]  Chi-Tang Ho,et al.  Stability of tea polyphenol (-)-epigallocatechin-3-gallate and formation of dimers and epimers under common experimental conditions. , 2005, Journal of agricultural and food chemistry.

[65]  A. Girotti,et al.  Superoxide and hydrogen peroxide-dependent lipid peroxidation in intact and triton-dispersed erythrocyte membranes. , 1984, Biochemical and biophysical research communications.

[66]  J. Gutteridge,et al.  Free Radicals and Iron: Chemistry, Biology, and Medicine , 1998 .

[67]  N. Manabe,et al.  The effect of feeding piglets with the diet containing green tea extracts or coumarin on in vitro metabolism of aflatoxin B1 by their tissues. , 2007, Toxicon : official journal of the International Society on Toxinology.

[68]  Y. Surh,et al.  Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[69]  Z. Selvanayagam,et al.  Gene expression changes induced by green tea polyphenol (-)-epigallocatechin-3-gallate in human bronchial epithelial 21BES cells analyzed by DNA microarray. , 2004, Molecular cancer therapeutics.

[70]  Yan-qing Li,et al.  Inhibition of Epigallocatechin Gallate on Orthotopic Colon Cancer by Upregulating the Nrf2-UGT1A Signal Pathway in Nude Mice , 2007, Pharmacology.

[71]  W. Berger,et al.  Green tea extract and (−)‐epigallocatechin‐3‐gallate, the major tea catechin, exert oxidant but lack antioxidant activities , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[72]  R. Dean,et al.  Radical chemistry of epigallocatechin gallate and its relevance to protein damage. , 2003, Archives of biochemistry and biophysics.

[73]  S. Aust,et al.  Transition metals as catalysts of "autoxidation" reactions. , 1990, Free radical biology & medicine.

[74]  S. Mettler,et al.  Effects of 3-week consumption of green tea extracts on whole-body metabolism during cycling exercise in endurance-trained men. , 2009, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[75]  Y. Hara,et al.  Antioxidant Potential of Gallocatechins. A Pulse Radiolysis and Laser Photolysis Study , 1995 .