Overcoming Drug Resistance by Phytochemicals

  • Marion M. ChanEmail author
  • Dunne Fong


Cancer drug resistance is a major cause of treatment failure. Various cancer chemopreventive phytochemicals can sensitize chemoresistant and radioresistant cancer cells. From in vitro tissue culture and in vivo xenograft studies with drug-resistant human cancer cell lines, synergistic effects have been shown between cancer therapeutics and molecules isolated from the spice turmeric, the beverages such as green tea and red wine, other sources of dietary fruits, vegetables, and grains, as well as herbal medicine. However, concerns on safety and bio-accessibility must be addressed further, and the proof-of-concept clinical data, to date, are still missing.


Phytochemicals Synergy Combination therapy Cancer prevention Epigallocatechin gallate Curcumin Resveratrol Cancer stem cells 



We thank Arthur Yeh for reading the manuscript. The writing of this chapter was supported, in part, by an award from the American Institute for Cancer Research to Marion Chan.


  1. Adapala, N., Chan, M.M. 2008. Long-term use of an antiinflammatory, curcumin, suppressed type 1 immunity and exacerbated visceral leishmaniasis in a chronic experimental model. Lab Invest. 88:1329–1339.Google Scholar
  2. Aggarwal, B.B., Shishodia, S. 2006a. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol. 71:1397–1421.PubMedCrossRefGoogle Scholar
  3. Aggarwal, B.B., Shishodia, S. Editors. 2006b. Resveratrol in Health and Disease. Boca Raton: Taylor& Francis.Google Scholar
  4. Aggarwal, B.B., Surh, Y.J., Shishodia, S. Editors. 2007. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. New York: Springer.CrossRefGoogle Scholar
  5. Aggarwal, B.B., Shishodia, S., Takada, Y., Banerjee, S., Newman, R.A., Bueso-Ramos, C.E., Price, J.E. 2005. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin. Cancer Res. 11:7490–7498.PubMedCrossRefGoogle Scholar
  6. Anand, P., Kunnumakkara, A.B., Newman, R.A., Aggarwal, B.B. 2007. Bioavailability of curcumin: problems and promises. Mol. Pharm. 4:807–818.PubMedCrossRefGoogle Scholar
  7. Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A.B., Aggarwal, B.B. 2008. Curcumin and cancer: An “old-age” disease with an “age-old” solution. Cancer Lett. 267:133–164.PubMedCrossRefGoogle Scholar
  8. Andreadi, C.K., Howells, L.M., Atherfold, P.A., Manson, M.M. 2006. Involvement of Nrf2, p38, B-Raf, and nuclear factor-kappaB, but not phosphatidylinositol 3-kinase, in induction of hemeoxygenase-1 by dietary polyphenols. Mol. Pharmacol. 69:1033–1040.PubMedGoogle Scholar
  9. Athar, M., Back, J.H., Tang, X., Kim, K.H., Kopelovich, L., Bickers, D.R., Kim, A.L. 2007. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol. Appl. Pharmacol. 224:274–283.PubMedCrossRefGoogle Scholar
  10. Awad, A.B., Bradford, P.G., Editors. 2005. Nutrition and Cancer Prevention. Boca Raton: Taylor & Francis.Google Scholar
  11. Balasubramanian, S., Eckert, R.L. 2007. Keratinocyte proliferation, differentiation, and apoptosis – differential mechanisms of regulation by curcumin, EGCG and apigenin. Toxicol. Appl. Pharmacol. 224:214–219.PubMedCrossRefGoogle Scholar
  12. Banerjee, S., Li, Y., Wang, Z., Sarkar, F.H. 2008. Multi-targeted therapy of cancer by genistein. Cancer Lett. 269:226–242.Google Scholar
  13. Banerjee, S., Zhang, Y., Wang, Z., Che, M., Chiao, P.J., Abbruzzese, J.L., Sarkar, F.H. 2007. In vitro and in vivo molecular evidence of genistein action in augmenting the efficacy of cisplatin in pancreatic cancer. Int. J. Cancer. 120:906–917.PubMedCrossRefGoogle Scholar
  14. Banerjee, S., Zhang, Y., Ali, S., Bhuiyan, M., Wang, Z., Chiao, P.J., Philip, P.A., Abbruzzese, J., Sarkar, F.H. 2005. Molecular evidence for increased antitumor activity of gemcitabine by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer. Cancer Res. 65:9064–9072.PubMedCrossRefGoogle Scholar
  15. Barger, J.L., Kayo, T., Vann, J.M., Arias, E.B., Wang, J., Hacker, T.A., Wang, Y., Raederstorff, D., Morrow, J.D., Leeuwenburgh, C., Allison, D.B., Saupe, K.W., Cartee, G.D., Weindruch, R., Prolla, T.A. 2008. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE. 3:e2264.PubMedCrossRefGoogle Scholar
  16. Barve, A., Khor, T.O., Hao, X., Keum, Y.S., Yang, C.S., Reddy, B., Kong, A.N. 2008. Murine Prostate Cancer Inhibition by Dietary Phytochemicals-Curcumin and Phenyethylisothiocyanate. Pharm. Res. 25:2181–2189.Google Scholar
  17. Baur, J.A., Sinclair, D.A. 2006. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 5:493–506.PubMedCrossRefGoogle Scholar
  18. Baur, J.A., Pearson, K.J., Price, N.L., Jamieson, H.A., Lerin, C., Kalra, A., Prabhu, V.V., Allard, J.S., Lopez-Lluch, G., Lewis, K., Pistell, P.J., Poosala, S., Becker, K.G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K.W., Spencer, R.G., Lakatta, E.G., Le Couteur, D., Shaw, R.J., Navas, P., Puigserver, P., Ingram, D.K., de Cabo, R., Sinclair, D.A. 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 444:337–342.PubMedCrossRefGoogle Scholar
  19. Bhardwaj, A., Sethi, G., Vadhan-Raj, S., Bueso-Ramos, C., Takada, Y., Gaur, U., Nair, A.S., Shishodia, S., Aggarwal, B.B. 2007. Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood. 109:2293–2302.PubMedCrossRefGoogle Scholar
  20. Bickenbach, K.A., Veerapong, J., Shao, M.Y., Mauceri, H.J., Posner, M.C., Kron, S.J., Weichselbaum, R.R. 2008. Resveratrol is an effective inducer of CArG-driven TNF-alpha gene therapy. Cancer Gene. Ther. 15:133–139.PubMedCrossRefGoogle Scholar
  21. Block, G., Patterson, B., Subar, A. 1992. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr. Cancer. 18:1–29.PubMedCrossRefGoogle Scholar
  22. Blumenthal, M. 2007. FDA approves special green tea extract as a new topical drug for genital warts: Expert says development marks the birth of a “new industry.” HerbalGram 74: 62–63.Google Scholar
  23. Boocock, D.J., Faust, G.E., Patel, K.R., Schinas, A.M., Brown, V.A., Ducharme, M.P., Booth, T.D., Crowell, J.A., Perloff, M., Gescher, A.J., Steward, W.P., Brenner, D.E. 2007. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol. Biomarkers Prev. 16:1246–1252.CrossRefGoogle Scholar
  24. Boots, A.W., Haenen, G.R., Bast, A. 2008. Health effects of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol. 585:325–337.PubMedCrossRefGoogle Scholar
  25. Calabrese, E.J. 2004. Hormesis: from marginalization to mainstream: a case for hormesis as the default dose-response model in risk assessment. Toxicol. Appl. Pharmacol. 197:125–136.PubMedCrossRefGoogle Scholar
  26. Calabrese, E.J., Baldwin, L.A. 2001. Hormesis: U-shaped dose responses and their centrality in toxicology. Trends Pharmacol. Sci. 22:285–291.PubMedCrossRefGoogle Scholar
  27. Carter, A. 2008. Curry compound fights cancer in the clinic. J. Natl. Cancer Inst. 100:616–617.PubMedCrossRefGoogle Scholar
  28. Cavaliere, C., Rea, P., Blumenthal, M. 2008. Herbal supplement sales in United States show growth in all channels. Herbal Gram 78:60–63.Google Scholar
  29. Chambers, A.F. 2009. Influence of diet on metastasis and tumor dormancy. Clin. Exp. Metastasis. 26:61–66.Google Scholar
  30. Chan, M.M. 1995. Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem. Pharmacol. 49:1551–1556.PubMedCrossRefGoogle Scholar
  31. Chan, M.M. 2002. Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of the skin. Biochem. Pharmacol. 63:99–104.PubMedCrossRefGoogle Scholar
  32. Chan, M.M., Fong, D. 1999. Modulation of the nitric oxide pathway by natural products. In Cellular and Molecular Biology of Nitric Oxide, eds. J.D. Laskin and D.L. Laskin, pp. 333–351, New York: Marcel Dekker, Inc.Google Scholar
  33. Chan, M.M., Fong, D. 2007a. Overcoming ovarian cancer drug resistance with phytochemicals and other compounds. In Cancer Drug Resistance Research Perspectives, ed. L.S. Torres, pp. 173–201, Hauppauge: Nova Science Publishers.Google Scholar
  34. Chan, M.M., Fong, D. 2007b. Overcoming ovarian cancer drug resistance with phytochemicals and other compounds. In Progress in Cancer Drug Resistance Research, ed. R.A. Parsons, pp. 1–28 , Hauppauge: Nova Science Publishers.Google Scholar
  35. Chan, M.M., Fong, D., Ho, C.T., Huang, H.I. 1997. Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem. Pharmacol. 54:1281–1286.PubMedCrossRefGoogle Scholar
  36. Chan, M.M., Huang, H.I., Fenton, M.R., Fong, D. 1998. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem. Pharmacol. 55:1955–1962.PubMedCrossRefGoogle Scholar
  37. Chan, M.M., Fong, D., Soprano, K.J., Holmes, W.F., Heverling, H. 2003.Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J. Cell Physiol. 194:63–70.PubMedCrossRefGoogle Scholar
  38. Chan, M.M., Mattiacci, J.A., Hwang, H.S., Shah, A., Fong, D. 2000. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem. Pharmacol. 60:1539–1548.PubMedCrossRefGoogle Scholar
  39. Chan, M.M., Soprano, K.J., Weinstein, K., Fong, D. 2006. Epigallocatechin-3-gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility. J Cell Physiol. 207:389–396.Google Scholar
  40. Chen, X., Yang, L., Oppenheim, J.J., Howard, M.Z. 2002. Cellular pharmacology studies of shikonin derivatives. Phytother. Res. 16:199–209.PubMedCrossRefGoogle Scholar
  41. Cheze, C., Vercauteren, J., Verpoorte, R. Editors. 2001. Polyphenols, Wine and Health. Dordrecht: Kluwer Academic Publishers.Google Scholar
  42. Chien, J.R., Aletti, G., Bell, D.A., Keeney, G.L., Shridhar, V., Hartmann, L.C. 2007. Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer. J. Cell. Biochem. 102: 1117–1129.PubMedCrossRefGoogle Scholar
  43. Chinnery, P.F., Howell, N., Lightowlers, R.N., Turnbull, D.M. 1997. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain. 120:1713–1721.PubMedCrossRefGoogle Scholar
  44. Choi, B.H., Kim, C.G., Lim, Y., Shin, S.Y., Lee, Y.H. 2008. Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway. Cancer Lett. 259:111–118.PubMedCrossRefGoogle Scholar
  45. Choi, S.W., Friso, S. Editors. 2006. Nutrient-Gene Interactions in Cancer. Boca Raton: Taylor & Francis.CrossRefGoogle Scholar
  46. Christensen, J.G., LeBlanc, G.A. 1996. Reversal of multidrug resistance in vivo by dietary administration of the phytochemical indole-3-carbinol. Cancer Res. 56:574–581.PubMedGoogle Scholar
  47. Das, D.K., Ursini, F. 2002. Alcohol and Wine in Health and Disease. New York: New York Academy of Sciences.Google Scholar
  48. Dean, M., Fojo, T., Bates, S. 2005. Tumour stem cells and drug resistance. Nat. Rev. Cancer. 5:275–284.PubMedCrossRefGoogle Scholar
  49. Dechsupa, S., Kothan, S., Vergote, J., Leger, G., Martineau, A., Berangeo, S., Kosanlavit, R., Moretti, J.L., Mankhetkorn, S. 2007. Quercetin, Siamois 1 and Siamois 2 induce apoptosis in human breast cancer MDA-mB-435 cells xenograft in vivo. Cancer Biol. Ther. 6:56–61.PubMedCrossRefGoogle Scholar
  50. de la Lastra, C.A., Villegas, I. 2007. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem. Soc. Trans. 35:1156–1160.PubMedCrossRefGoogle Scholar
  51. De Smet, P.A. 2007. Clinical risk management of herb-drug interactions. Br. J. Clin. Pharmacol. 63:258–267.PubMedCrossRefGoogle Scholar
  52. D‘Incalci, M, Steward, W.P., Gescher, A.J. 2005. Use of cancer chemopreventive phytochemicals as antineoplastic agents. Lancet Oncol. 6:899–904.PubMedCrossRefGoogle Scholar
  53. Donnenberg, V.S., Donnenberg, A.D. 2005. Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J. Clin. Pharmacol. 45:872–877.PubMedCrossRefGoogle Scholar
  54. Dorai, T., Aggarwal, B.B. 2004. Role of chemopreventive agents in cancer therapy. Cancer Lett. 215:129–140.PubMedCrossRefGoogle Scholar
  55. Duvoix, A., Blasius, R., Delhalle, S., Schnekenburger, M., Morceau, F., Henry, E., Dicato, M., Diederich, M. 2005. Chemopreventive and therapeutic effects of curcumin. Cancer Lett. 223:181–190.PubMedCrossRefGoogle Scholar
  56. Espín, J.C., García-Conesa, M.T., Tomás-Barberán, F.A. 2007. Nutraceuticals: facts and fiction. Phytochemistry. 68:2986–3008.PubMedCrossRefGoogle Scholar
  57. Fojo, T. 2008. Commentary: Novel therapies for cancer: why dirty might be better. Oncologist. 13:277–283.PubMedCrossRefGoogle Scholar
  58. Francy-Guilford, J., Pezzuto, J.M. 2008. Mechanisms of Cancer Chemopreventive Agents: A Perspective. Planta Med. 74:1644–1650.Google Scholar
  59. Fulda, S., Debatin, K.M. 2004. Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent resveratrol. Oncogene. 23:6702–6711.PubMedCrossRefGoogle Scholar
  60. Fulda, S., Debatin, K.M. 2006. Resveratrol modulation of signal transduction in apoptosis and cell survival: a mini-review. Cancer Detect. Prev. 30:217–223.PubMedCrossRefGoogle Scholar
  61. Galati, G., and O’Brien, P.J. 2004. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic. Biol. Med. 37: 287–303.PubMedCrossRefGoogle Scholar
  62. Garcea, G., Berry, D.P., Jones, D.J., Singh, R., Dennison, A.R., Farmer, P.B., Sharma, R.A., Steward, W.P., Gescher, A.J. 2005. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol. Biomarkers Prev. 14:120–125.PubMedGoogle Scholar
  63. Garg, A.K., Buchholz, T.A., Aggarwal, B.B. 2005. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid. Redox Signal. 7:1630–1647.PubMedCrossRefGoogle Scholar
  64. Garvin, S., Ollinger, K., Dabrosin, C. 2006. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett. 231:113–122.PubMedCrossRefGoogle Scholar
  65. Gescher, A.J. 2008. Resveratrol from_red grapes – pedestrian polyphenol or useful anticancer agent? Planta Med. 74:1651–1655.Google Scholar
  66. Goel, A., Jhurani, S., Aggarwal, B.B. 2008. Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res. 52:1010–1030.Google Scholar
  67. Goel, A., Kunnumakkara, A.B., Aggarwal, B.B. 2008. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol. 75:787–809.PubMedCrossRefGoogle Scholar
  68. Gross, G., Meyer, K.G., Pres, H., Thielert, C., Tawfik, H., Mescheder, A. 2007. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon E in the treatment of external genital warts. J Eur Acad Dermatol Venereol. 21:1404–1412.PubMedCrossRefGoogle Scholar
  69. Halls, C., Yu, O. 2008. Potential for metabolic engineering of resveratrol biosynthesis. Trends Biotechnol. 26:77–81.PubMedCrossRefGoogle Scholar
  70. Han, W., Li, L., Qiu, S., Lu, Q., Pan, Q., Gu, Y., Luo, J., Hu, X. 2007. Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol. Cancer Ther. 6:1641–1649.PubMedCrossRefGoogle Scholar
  71. Hanahan, D., Weinberg, R.A. 2000. The hallmarks of cancer. Cell. 100:57–70.PubMedCrossRefGoogle Scholar
  72. Hara, Y. 2001. Green Tea: Health Benefits and Applications. New York: Marcel Dekker, Inc.CrossRefGoogle Scholar
  73. Harikumar, K.B., Aggarwal, B.B. 2008. Resveratrol: a multitargeted agent for age-associated chronic diseases. Cell Cycle. 7:1020–1035.PubMedCrossRefGoogle Scholar
  74. Harwood, M., Danielewska-Nikiel, B., Borzelleca, J.F., Flamm, G.W., Williams, G.M., Lines, T.C. 2007. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol. 45:2179–2205.PubMedCrossRefGoogle Scholar
  75. HemaIswarya, S., Doble, M. 2006. Potential synergism of natural products in the treatment of cancer. Phytother. Res. 20:239–249.PubMedCrossRefGoogle Scholar
  76. Higdon, J. 2007. An Evidence-Based Approach to Dietary Phytochemicals. New York:Thieme.Google Scholar
  77. Hour, T.C., Chen, J., Huang, C.Y., Guan, J.Y., Lu, S.H., Pu, Y.S. 2002. Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. Prostate. 51:211–218.PubMedCrossRefGoogle Scholar
  78. Howells, L.M., Mitra, A., Manson, M.M. 2007. Comparison of oxaliplatin- and curcumin-mediated antiproliferative effects in colorectal cell lines. Int. J. Cancer. 121:175–183.PubMedCrossRefGoogle Scholar
  79. Hu, Z.Q., Zhao, W.H., Asano, N., Yoda, Y., Hara, Y., Shimamura, T. 2002. Epigallocatechin gallate synergistically enhances the activity of carbapenems against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 46:558–560.PubMedCrossRefGoogle Scholar
  80. Hu, X., Xuan, Y. 2008. Bypassing cancer drug resistance by activating multiple death pathways – a proposal from the study of circumventing cancer drug resistance by induction of necroptosis. Cancer Lett. 259:127–137.PubMedCrossRefGoogle Scholar
  81. Hwang, J.T., Ha, J., Park, O.J. 2005. Combination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX-2 signaling pathways. Biochem. Biophys. Res. Commun. 332:433–440.PubMedCrossRefGoogle Scholar
  82. Hwang, J.T., Kwak, D.W., Lin, S.K., Kim, H.M., Kim, Y.M., Park, O.J. 2007. Resveratrol induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling pathway. Ann. N. Y. Acad. Sci. 1095:441–448.PubMedCrossRefGoogle Scholar
  83. Israelsen, L. 2008. Resveratrol granted orphan drug status. Neutraceuticals World 11:15.Google Scholar
  84. Ivanov, V.N., Partridge, M.A., Johnson, G.E., Huang, S.X., Zhou, H., Hei, T.K. 2008. Resveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression. Exp. Cell Res. 314:1163–1176.PubMedCrossRefGoogle Scholar
  85. Izzo, A.A. 2005. Herb-drug interactions: an overview of the clinical evidence. Fundam. Clin. Pharmacol. 19:1–16.PubMedCrossRefGoogle Scholar
  86. Jatoi, A., Ellison, N., Burch, P.A., Sloan, J.A., Dakhil, S.R., Novotny, P., Tan, W., Fitch, T.R., Rowland, K.M., Young, C.Y., Flynn, P.J. 2003. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer. 97: 1442–1446.PubMedCrossRefGoogle Scholar
  87. Jayaraman, K.S. 1997. US patent office withdraws patent on Indian herb. Nature. 389:6.CrossRefGoogle Scholar
  88. Kawanishi, S., Oikawa, S., Murata, M. 2005. Evaluation for safety of antioxidant chemopreventive agents. Antioxid. Redox Signal. 7:1728–1739.PubMedCrossRefGoogle Scholar
  89. Keith, C.T., Borisy, A.A., Stockwell, B.R. 2005. Multicomponent therapeutics for networked systems. Nat. Rev. Drug Discov. 4:71–78.PubMedCrossRefGoogle Scholar
  90. Khan, N., Mukhtar, H. 2007. Tea polyphenols for health promotion. Life Sci. 81:519–533.PubMedCrossRefGoogle Scholar
  91. Khan, N., Mukhtar, H. 2008. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 269:269–280.Google Scholar
  92. Khan, N., Afaq, F., Saleem, M., Ahmad, N., Mukhtar, H. 2006. Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. Cancer Res. 66:2500–2505.PubMedCrossRefGoogle Scholar
  93. Kris-Etherton, P.M., Hecker, K.D., Bonanome, A., Coval, S.M., Binkoski, A.E., Hilpert, K.F., Griel, A.E., Etherton, T.D. 2002. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am. J. Med. 113:71S–88S.PubMedCrossRefGoogle Scholar
  94. Kroemer, G., Pouyssegur, J. 2008. Tumor cell metabolism: cancer‘s Achilles‘ heel. Cancer Cell. 13:472–482.PubMedCrossRefGoogle Scholar
  95. Kundu, J.K., Surh, Y.J. 2008. Cancer chemopreventive and therapeutic potential of resveratrol: Mechanistic perspectives. Cancer Lett. 269:243–261.Google Scholar
  96. Kunnumakkara, A.B., Anand, P., Aggarwal, B.B. 2008. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 269:199–225.Google Scholar
  97. Kunnumakkara, A.B., Guha, S., Krishnan, S., Diagaradjane, P., Gelovani, J., Aggarwal, B.B. 2007. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 67:3853–3861.PubMedCrossRefGoogle Scholar
  98. Kuriyama, S., Shimazu, T., Ohmori, K., Kikuchi, N., Nakaya, N., Nishino, Y., Tsubono, Y., Tsuji, I. 2006. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA. 296:1255–1265.PubMedCrossRefGoogle Scholar
  99. Lambert, J.D., Hong, J., Kim, D.H., Mishin, V.M., Yang, C.S. 2004. Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice. J. Nutr. 134:1948–1952.PubMedGoogle Scholar
  100. Lambert, J.D., Hong, J., Yang, G.Y., Liao, J., Yang, C.S. 2005. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am. J. Clin. Nutr. 81:284S–291S.PubMedGoogle Scholar
  101. Landis-Piwowar, K.R., Huo, C., Chen, D., Milacic, V., Shi, G., Chan, T.H., Dou, Q.P. 2007. A novel prodrug of the green tea polyphenol (-)-epigallocatechin-3-gallate as a potential anticancer agent. Cancer Res. 67:4303–4310.PubMedCrossRefGoogle Scholar
  102. Larsson, S.C., Wolk, A. 2005. Tea consumption and ovarian cancer risk in a population-based cohort. Arch. Intern. Med. 165:2683–2386.PubMedCrossRefGoogle Scholar
  103. Li, Y., Ahmed, F., Ali, S., Philip, P.A., Kucuk, O., Sarkar, F.H. 2005. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res. 2005 65:6934–6942.CrossRefGoogle Scholar
  104. Limtrakul, P., Chearwae, W., Shukla, S., Phisalphong, C., Ambudkar, S.V. 2007. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin. Mol Cell Biochem. 296:85–95.PubMedCrossRefGoogle Scholar
  105. Lin, Y.G., Kunnumakkara, A.B., Nair, A., Merritt, W.M., Han, L.Y., Armaiz-Pena, G.N., Kamat, A.A., Spannuth, W.A., Gershenson, D.M., Lutgendorf, S.K., Aggarwal, B.B., Sood, A.K. 2007. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin. Cancer Res. 2007 13:3423–3430.CrossRefGoogle Scholar
  106. Lobo, N.A., Shimono, Y., Qian, D., Clarke, M.F. 2007. The biology of cancer stem cells. Annu. Rev. Cell Dev. Biol. 23:675–699.PubMedCrossRefGoogle Scholar
  107. Maheshwari, R.K., Singh, A.K., Gaddipati, J., Srimal, R.C. 2006. Multiple biological activities of curcumin: a short review. Life Sci. 78:2081–2087.PubMedCrossRefGoogle Scholar
  108. Mai, Z., Blackburn, G.L., Zhou, J.R. 2007. Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Mol. Carcinog. 46:534–542.PubMedCrossRefGoogle Scholar
  109. Manson, M.M. 2003. Cancer prevention – the potential for diet to modulate molecular signalling. Trends Mol. Med. 9:11–18.PubMedCrossRefGoogle Scholar
  110. Manson, M.M., Foreman, B.E., Howells, L.M., Moiseeva, E.P. 2007. Determining the efficacy of dietary phytochemicals in cancer prevention. Biochem. Soc. Trans. 35:1358–1363.PubMedCrossRefGoogle Scholar
  111. Martínez-Lacaci, I., García Morales, P., Soto, J.L., Saceda, M. 2007. Tumour cells resistance in cancer therapy. Clin. Transl. Oncol. 9:13–20.PubMedCrossRefGoogle Scholar
  112. Mathijssen, R.H., Verweij, J., de Bruijn, P., Loos, W.J., Sparreboom, A. 2002. Effects of St. John‘s wort on irinotecan metabolism. J. Natl. Cancer Inst. 94:1247–1249.PubMedCrossRefGoogle Scholar
  113. Mattson, M.P. 2008. Dietary factors, hormesis and health. Ageing Res. Rev. 7:43–48.PubMedCrossRefGoogle Scholar
  114. McEligot, A.J., Yang, S., Meyskens, F.L. Jr. 2005. Redox regulation by intrinsic species and extrinsic nutrients in normal and cancer cells. Annu. Rev. Nutr. 25:261–295.PubMedCrossRefGoogle Scholar
  115. Meijerman, I., Beijnen, J.H., Schellens, J.H. 2006. Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist. 11:742–752.PubMedCrossRefGoogle Scholar
  116. Manach, C., Williamson, G., Morand, C., Scalbert, A., Rémésy, C. 2005. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 81:230S–242S.PubMedGoogle Scholar
  117. Mencher, S.K., Wang, L.G. 2005. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin. Pharmacol. 5:3.PubMedCrossRefGoogle Scholar
  118. Meschini, S., Condello, M., Marra, M., Formisano, G., Federici, E., Arancia, G. 2007. Autophagy-mediated chemosensitizing effect of the plant alkaloid voacamine on multidrug resistant cells. Toxicol. In Vitro. 21:197–203.PubMedCrossRefGoogle Scholar
  119. Mohammad, R.M., Banerjee, S., Li, Y., Aboukameel, A., Kucuk, O., Sarkar, F.H. 2006. Cisplatin-induced antitumor activity is potentiated by the soy isoflavone genistein in BxPC-3 pancreatic tumor xenografts. Cancer. 106:1260–1268.PubMedCrossRefGoogle Scholar
  120. Moiseeva, E.P., Almeida, G.M., Jones, G.D., Manson, M.M. 2007. Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. Mol. Cancer Ther. 6:3071–3079.PubMedCrossRefGoogle Scholar
  121. Moon, Y.J., Shin, B.S., An, G., Morris, M.E. 2008. Biochanin A inhibits breast cancer tumor growth in a murine Xenograft model. Pharm. Res. 25:2158–2163.Google Scholar
  122. Moutsatsou, P. 2007. The spectrum of phytoestrogens in nature: our knowledge is expanding. Hormones (Athens). 6:173–193.PubMedGoogle Scholar
  123. Murphy, L.L., King, M.L., Smith, K.A. 2008. Ginseng (Panax quinquefolius) augments doxorubicin-induced inhibition of human breast cancer cell proliferation and tumor growth: mechanism of action. Life Science Innovations (Sigma-Aldrich). 23:13–14.Google Scholar
  124. Nakahira, S., Nakamori, S., Tsujie, M., Takahashi, Y., Okami, J., Yoshioka, S., Yamasaki, M., Marubashi, S., Takemasa, I., Miyamoto, A., Takeda, Y., Nagano, H., Dono, K., Umeshita, K., Sakon, M., Monden, M. 2007. Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer. 120: 1355–1363.PubMedCrossRefGoogle Scholar
  125. Niles, R.M., Cook, C.P., Meadows, G.G., Fu, Y.M., McLaughlin, J.L., Rankin, G.O. 2006. Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit human melanoma xenograft tumor growth. J. Nutr. 136:2542–2546.PubMedGoogle Scholar
  126. Niles, R.M., McFarland, M., Weimer, M.B., Redkar, A., Fu, Y.M., Meadows, G.G. 2003. Resveratrol is a potent inducer of apoptosis in human melanoma cells. Cancer Lett. 190:157–163.PubMedCrossRefGoogle Scholar
  127. Nishikawa, T., Nakajima, T., Moriguchi, M., Jo, M., Sekoguchi, S., Ishii, M., Takashima, H., Katagishi, T., Kimura, H., Minami, M., Itoh, Y., Kagawa, K., Okanoue, T. 2006. A green tea polyphenol, epigallocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins. J. Hepatol. 44:1074–1082.PubMedCrossRefGoogle Scholar
  128. Ohori, H., Yamakoshi, H., Tomizawa, M., Shibuya, M., Kakudo, Y., Takahashi, A., Takahashi, S., Kato, S., Suzuki, T., Ishioka, C., Iwabuchi, Y., Shibata, H. 2006. Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer. Mol. Cancer Ther. 5:2563–2571.PubMedCrossRefGoogle Scholar
  129. Okada, H., Mak, T.W. 2004. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer. 4:592–603.PubMedCrossRefGoogle Scholar
  130. Opie, L.H., Lecour, S. 2007. The red wine hypothesis: from concepts to protective signalling molecules. Eur. Heart J. 28:1683–1693.PubMedCrossRefGoogle Scholar
  131. Orellana, C. 2003. Doubts cast on antimalarial drug. Lancet Infect. Dis. 3:61.PubMedCrossRefGoogle Scholar
  132. Pal, D., Mitra, A.K. 2006. MDR- and CYP3A4-mediated drug-drug interactions. J. Neuroimmune Pharmacol. 1:323–339.PubMedCrossRefGoogle Scholar
  133. Pan, M.H., Ghai, G., Ho, C.T. 2008. Food bioactives, apoptosis, and cancer. Mol. Nutr. Food Res. 52:43–52.PubMedCrossRefGoogle Scholar
  134. Pan, M.H., Gao, J.H., Lai, C.S., Wang, Y.J., Chen, W.M., Lo, C.Y., Wang, M., Dushenkov, S., Ho, C.T. 2008. Antitumor activity of 3,5,4‘-trimethoxystilbene in COLO 205 cells and xenografts in SCID mice. Mol. Carcinog. 47:184–196.PubMedCrossRefGoogle Scholar
  135. Parr, A.J., Bolwell, G.P. 2000. Phenols in the plant and in man. The potential for possible nutritional enhancement of the diet by modifying the phenols content or profile. J. Sci. Food Agric. 80:985–1012.CrossRefGoogle Scholar
  136. Pearson, K.J., Baur, J.A., Lewis, K.N., Peshkin, L., Price, N.L., Labinskyy, N., Swindell, W.R., Kamara, D., Minor, R.K., Perez, E., Jamieson, H.A., Zhang, Y., Dunn, S.R., Sharma, K., Pleshko, N., Woollett, L.A., Csiszar, A., Ikeno, Y., Le Couteur, D., Elliott, P.J., Becker, K.G., Navas, P., Ingram, D.K., Wolf, N.S., Ungvari, Z., Sinclair, D.A., de Cabo, R. 2008 Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction Without Extending Life Span.Cell Metab. 8:157–168.Google Scholar
  137. Pirola, L., Fröjdö, S. 2008. Resveratrol: one molecule, many targets. IUBMB Life. 60:323–332.PubMedCrossRefGoogle Scholar
  138. Rahman, I., Biswas, S.K., Kirkham, P.A. 2006. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem. Pharmacol. 72:1439–1452.PubMedCrossRefGoogle Scholar
  139. Raj, M.H., Abd Elmageed, Z.Y., Zhou, J., Gaur, R., Nguyen, L., Azam, G.A., Braley, P., Rao, P.N., Fathi, I.M., Ouhtit, A. 2008. Synergistic action of dietary phyto-antioxidants on survival and proliferation of ovarian cancer cells. Gynecol Oncol. 110:432–438.Google Scholar
  140. Rapaka, R.S., Coates, P.M. 2006. Dietary supplements and related products: a brief summary. Life Sci. 78:2026–2032.PubMedCrossRefGoogle Scholar
  141. Ravindranath, M.H., Saravanan, T.S., Monteclaro, C.C., Presser, N., Ye, X., Selvan, S.R., Brosman, S. 2006. Epicatechins Purified from Green Tea (Camellia sinensis) Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines. Evid. Based Complement Alternat. Med. 3:237–247.PubMedCrossRefGoogle Scholar
  142. Rezk, Y.A., Balulad, S.S., Keller, R.S., Bennett, J.A. 2006. Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart. Am. J. Obstet .Gynecol. 194:e23–e26.PubMedCrossRefGoogle Scholar
  143. Russo, G.L. 2007. Ins and outs of dietary phytochemicals in cancer chemoprevention. Biochem. Pharmacol. 74:533–544.PubMedCrossRefGoogle Scholar
  144. Russo, M., Nigro, P., Rosiello, R., D‘Arienzo, R., Russo, G.L. 2007. Quercetin enhances CD95- and TRAIL-induced apoptosis in leukemia cell lines. Leukemia. 21:1130–1133.PubMedGoogle Scholar
  145. Saiko, P., Szakmary, A., Jaeger, W., Szekeres, T. 2008. Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat. Res. 658:68–94.Google Scholar
  146. Sallman, D.A., Chen, X., Zhong, B., Gilvary, D.L., Zhou, J., Wei, S., Djeu, J.Y. 2007. Clusterin mediates TRAIL resistance in prostate tumor cells. Mol. Cancer Ther. 6:2938–2947.PubMedCrossRefGoogle Scholar
  147. Salvioli, S., Sikora, E., Cooper, E.L., Franceschi, C. 2007. Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies. Evid. Based Complement Alternat. Med. 4:181–190.PubMedCrossRefGoogle Scholar
  148. Sareen, D., Darjatmoko, S.R., Albert, D.M., Polans, A.S. 2007. Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer. Mol. Pharmacol. 72: 1466–1475.PubMedCrossRefGoogle Scholar
  149. Sarkar, F.H., Li, Y. 2006. Using chemopreventive agents to enhance the efficacy of cancer therapy. Cancer Res. 66:3347–3350.PubMedCrossRefGoogle Scholar
  150. Schlachterman, A., Valle, F., Wall, K.M., Azios, N.G., Castillo, L., Morell, L., Washington, A.V., Cubano, L.A., Dharmawardhane, S.F. 2008. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl. Oncol. 1:19–27.PubMedGoogle Scholar
  151. Scholz, S., Williamson, G. 2007. Interactions affecting the bioavailability of dietary polyphenols in vivo. Int. J. Vitam. Nutr. Res. 77:224–235.PubMedCrossRefGoogle Scholar
  152. Seeram, N.P. 2008. Berry fruits for cancer prevention: current status and future prospects. J. Agric. Food Chem. 56:630–635.PubMedCrossRefGoogle Scholar
  153. Shankar, S., Ganapathy, S., Chen, Q., Srivastava, R.K. 2008. Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol. Cancer. 7:16.PubMedCrossRefGoogle Scholar
  154. Shanmugam, K., Holmquist, L., Steele, M., Stuchbury, G., Berbaum, K., Schulz, O., Benavente García, O., Castillo, J., Burnell, J., Garcia Rivas, V., Dobson, G., Münch, G. 2008. Plant-derived polyphenols attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages. Mol. Nutr. Food Res. 52:427–438.PubMedCrossRefGoogle Scholar
  155. Sharma, R.A., Gescher, A.J., Steward, W.P. 2005. Curcumin: the story so far. Eur. J. Cancer. 41:1955–1968.PubMedCrossRefGoogle Scholar
  156. Shen, J., Tai, Y.C., Zhou, J., Stephen Wong, C.H., Cheang, P.T., Fred Wong, W.S., Xie, Z., Khan, M., Han, J.H., Chen, C.S. 2007. Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft model and potential mechanism through MAPK signaling. Exp. Hematol. 35:75–83.PubMedGoogle Scholar
  157. Shervington, A., Pawar, V., Menon, S., Thakkar, D., Patel, R. 2008. The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin. Mol. Biol. Rep. Jun 26. [Epub ahead of print]Google Scholar
  158. Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., Srinivas, P.S. 1998. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 64: 353–356.PubMedCrossRefGoogle Scholar
  159. Soleas, G.J., Diamandis, E.P., Goldberg, D.M. 1997a. Resveratrol: a molecule whose time has come? And gone? Clin Biochem. 30:91–113.PubMedCrossRefGoogle Scholar
  160. Soleas, G.J., Diamandis, E.P., Goldberg, D.M. 1997b. Wine as a biological fluid: history, production, and role in disease prevention. J. Clin. Lab. Anal. 11:287–313.PubMedCrossRefGoogle Scholar
  161. Somasundaram, S., Edmund, N.A., Moore, D.T., Small, G.W., Shi, Y.Y., Orlowski, R.Z. 2002. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 62:3868–3875.PubMedGoogle Scholar
  162. Spinella, F., Rosanò, L., Di Castro, V., Decandia, S., Albini, A., Nicotra, M.R., Natali, P.G., Bagnato, A. 2006. Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma. Mol. Cancer Ther. 5:1483–1492.PubMedCrossRefGoogle Scholar
  163. Strimpakos, A.S., Sharma, R.A. 2008. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid. Redox Signal. 10:511–545.PubMedCrossRefGoogle Scholar
  164. Surh, Y.J. 2003. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer. 3:768–780.PubMedCrossRefGoogle Scholar
  165. Surh, Y.J., Kundu, J.K., Na, H.K., Lee, J.S. 2005. Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J. Nutr. 135:2993S–3001S.PubMedGoogle Scholar
  166. Tascilar, M., de Jong, F.A., Verweij, J., Mathijssen, R.H. 2006. Complementary and alternative medicine during cancer treatment: beyond innocence. Oncologist. 11:732–741.PubMedCrossRefGoogle Scholar
  167. Teicher, B.A., Editor. 2006. Cancer Drug Resistance. Totowa: Humana Press.Google Scholar
  168. Thomasset, S.C., Berry, D.P., Garcea, G., Marczylo, T., Steward, W.P., Gescher, A.J. 2007. Dietary polyphenolic phytochemicals–promising cancer chemopreventive agents in humans? A review of their clinical properties. Int. J. Cancer. 120:451–458.PubMedCrossRefGoogle Scholar
  169. Thompson, L.U., Ward, W.E. Editors. 2005. Food-Drug Synergy and Safety. Boca Raton: Taylor & Francis.CrossRefGoogle Scholar
  170. Trewavas, A., Stewart, D. 2003. Paradoxical effects of chemicals in the diet on health. Curr. Opin. Plant Biol. 6:185–190.PubMedCrossRefGoogle Scholar
  171. van Ginkel, P.R., Sareen, D., Subramanian, L., Walker, Q., Darjatmoko, S.R., Lindstrom, M.J., Kulkarni, A., Albert, D.M., Polans, A.S. 2007. Resveratrol inhibits tumor growth of human neuroblastoma and mediates apoptosis by directly targeting mitochondria. Clin. Cancer Res. 13:5162–5269.PubMedCrossRefGoogle Scholar
  172. Vantyghem, S.A., Wilson, S.M., Postenka, C.O., Al-Katib, W., Tuck, A.B., Chambers, A.F. 2005. Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model. Cancer Res. 65:3396–3403.PubMedGoogle Scholar
  173. Verschoyle, R.D., Steward, W.P., Gescher, A.J. 2007. Putative cancer chemopreventive agents of dietary origin-how safe are they? Nutr Cancer. 59:152–162.Google Scholar
  174. Wahl, H., Tan, L., Griffith, K., Choi, M., Liu, J.R. 2007. Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer cells. Gynecol. Oncol. 105:104–112.PubMedCrossRefGoogle Scholar
  175. Wang, T.T., Hudson, T.S., Wang, T.C., Remsberg, C.M., Davies, N.M., Takahashi, Y., Kim, Y.S., Seifried, H., Vinyard, B.T., Perkins, S.N., Hursting, S.D. 2008. Differential Effects of Resveratrol on Androgen-responsive LNCaP Human Prostate Cancer Cells In Vitro and In Vivo. Carcinogenesis. 29:2001–2010.Google Scholar
  176. Weir, N.M., Selvendiran, K., Kutala, V.K., Tong, L., Vishwanath, S., Rajaram, M., Tridandapani, S., Anant, S., Kuppusamy, P. 2007. Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol. Ther. 6:178–184.PubMedCrossRefGoogle Scholar
  177. Weng, J.R., Tsai, C.H., Kulp, S.K., Chen, C.S. 2008. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 262:153–163.PubMedCrossRefGoogle Scholar
  178. Williamson, G., Manach, C. 2005. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am. J. Clin. Nutr. 81:243S–255S.PubMedGoogle Scholar
  179. Wilson, T.R., Longley, D.B., Johnston, P.G. 2006. Chemoresistance in solid tumours. Ann. Oncol. 17:x315–324.PubMedCrossRefGoogle Scholar
  180. Wu, S.L., Sun, Z.J., Yu, L., Meng, K.W., Qin, X.L., Pan, C.E. 2004. Effect of resveratrol and in combination with 5-FU on murine liver cancer. World J. Gastroenterol. 10:3048–3052.PubMedGoogle Scholar
  181. Yang, C.S., Lambert, J.D., Ju, J., Lu, G., Sang, S. 2007a. Tea and cancer prevention: molecular mechanisms and human relevance. Toxicol. Appl. Pharmacol. 224:265–373.PubMedCrossRefGoogle Scholar
  182. Yang, C.S., Lambert, J.D., Hou, Z., Ju, J., Lu, G., Hao, X. 2006a. Molecular targets for the cancer preventive activity of tea polyphenols. Mol. Carcinog. 45:431–435.PubMedCrossRefGoogle Scholar
  183. Yang, C.S., Sang, S., Lambert, J.D., Hou, Z., Ju, J., Lu, G. 2006b. Possible mechanisms of the cancer-preventive activities of green tea. Mol. Nutr. Food Res. 50:170–175.PubMedCrossRefGoogle Scholar
  184. Yang, G., Shu, X.O., Li, H., Chow, W.H., Ji, B.T., Zhang, X., Gao, Y.T., Zheng, W. 2007b. Prospective cohort study of green tea consumption and colorectal cancer risk in women. Cancer Epidemiol. Biomarkers Prev. 16:1219–1223.PubMedCrossRefGoogle Scholar
  185. You, G., Morris, M.E., Editors, 2007. Drug Transporters. Hoboken: John Wiley & Sons.CrossRefGoogle Scholar
  186. You, M., Ma, X., Mukherjee, R., Farnsworth, N.R., Cordell, G.A., Kinghorn, A.D., Pezzuto, J.M. 1994. Indole alkaloids from Peschiera laeta that enhance vinblastine-mediated cytotoxicity with multidrug-resistant cells. J. Nat. Prod. 57:1517–1522.PubMedCrossRefGoogle Scholar
  187. Zaveri, N.T. 2006. Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications. Life Sci. 78:2073–2080.PubMedCrossRefGoogle Scholar
  188. Zhang, Q., Wei, D., Liu, J. 2004. In vivo reversal of doxorubicin resistance by (-)-epigallocatechin gallate in a solid human carcinoma xenograft. Cancer Lett. 208:179–186.PubMedCrossRefGoogle Scholar
  189. Zhang, X., Zhang, H., Tighiouart, M., Lee, J.E., Shin, H.J., Khuri, F.R., Yang, C.S., Chen, Z.G., Shin, D.M. 2008. Synergistic inhibition of head and neck tumor growth by green tea (-)-epigallocatechin-3-gallate and EGFR tyrosine kinase inhibitor. Int. J. Cancer. 123:1005–1014.PubMedCrossRefGoogle Scholar
  190. Zhen, Y. Editor. 2002. Tea: Bioactivity and Therapeutic Potential. London: Taylor & Francis.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyTemple University School of MedicinePhiladelphiaUSA
  2. 2.Department of Cell Biology and Neuroscience, RutgersThe State University of New JerseyPiscatawayUSA

Personalised recommendations