Bioactive Compounds and Cancer pp 589-611

Part of the Nutrition and Health book series (NH)

Mammary and Prostate Cancer Chemoprevention and Mechanisms of Action of Resveratrol and Genistein in Rodent Models

  • Timothy G. WhitsettJr
  • Leah M. Cook
  • Brijesh B. Patel
  • Curt E. Harper
  • Jun Wang
  • Coral A. Lamartiniere

Key Points

1. Almost 200,000 men and women in the United States will be diagnosed with prostate and breast cancers, respectively, this year alone. It has become increasingly clear that environmental exposures, including diet, influence the risk of both breast and prostate cancers.

2. Two natural polyphenols that have received much interest in the field of cancer prevention are genistein, an isoflavone component of soy, and resveratrol, a phytoalexin found in red grapes and red wine. Epidemiological and in vitro laboratory data suggest that these polyphenols may protect against breast and prostate cancers.

3. Using in vivo rodent models of breast and prostate cancers, our lab and others have shown that genistein and resveratrol, administered alone or in combination, can suppress both breast and prostate carcinogenesis.

4. Genistein, at concentrations resulting in serum levels comparable to humans on a high soy diet, suppressed mammary tumor multiplicity through enhanced mammary gland maturation and a reduction in the targets of mammary carcinogens. Genistein also reduced the incidence of aggressive prostate tumors in a transgenic mouse model of prostate cancer.

5. Resveratrol, administered in the diet, suppressed mammary tumor multiplicity and increased tumor latency. Reductions in mammary epithelial cell proliferation and increased apoptosis help to explain these mammary protective effects. Resveratrol was also able to reduce the incidence of poorly differentiated prostate tumors through modulation of cell proliferation and critical growth factor pathways in the rodent prostate.

6. Chemoprevention of both breast and prostate cancers with combinational genistein and resveratrol treatments was also demonstrated. Both resveratrol and genistein, alone and in combination, were effective at suppressing breast and prostate carcinogenesis using in vivo models.

Key Words

Chemoprevention genistein resveratrol breast cancer prostate cancer 


  1. 1.
    American Cancer Society. (2008) Cancer Facts & Figures. Atlanta: American Cancer Society.Google Scholar
  2. 2.
    Kuiper, G.G., Lemmen, J.G., Carlsson, B. et al. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252–63.PubMedCrossRefGoogle Scholar
  3. 3.
    Adlercreutz, H., and Mazur, W. (1997) Phyto-oestrogens and Western diseases. Ann Med 29, 95–120.PubMedGoogle Scholar
  4. 4.
    Barnes, S., and Lamartiniere, C.A. (2003) The role of phytoestrogens as cancer prevention agents. In: Kelloff G.J., Hawk E.T., Sigman C.C. eds. Cancer Chemoprevention. 359–69, NJ, USA: Humana Press Inc.Google Scholar
  5. 5.
    Sarkar, F.H., and Li, Y. (2002) Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev 21, 265–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Adlercreutz, H., Markkanen, H., and Watanabe, S. (1993) Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342, 1209–10.PubMedCrossRefGoogle Scholar
  7. 7.
    Baggott, J.E., Ha, T., Vaughn, W.H., Juliana, M.M., Hardin, J.M., and Grubbs, C.J. (1990) Effect of miso (Japanese soybean paste) and NaCl on DMBA-induced rat mammary tumors. Nutr Cancer 14, 103–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Barnes, S., Grubbs, C.J., Setchell, K.D.R., and Carlson, J. Soybeans Inhibit Mammary Tumors in Models of Breast Cancer. Wiley Liss: New York, USA; 1990.Google Scholar
  9. 9.
    Lamartiniere, C.A., Moore, J.B., Brown, N.M., Thompson, R., Hardin, M.J., and Barnes, S. (1995) Genistein suppresses mammary cancer in rats. Carcinogenesis 16, 2833–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Fritz, W.A., Coward, L., Wang, J., and Lamartiniere, C.A. (1998) Dietary genistein: Perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis 19, 2151–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Badger, T.M., Ronis, M.J., Hakkak, R., Rowlands, J.C., and Korourian, S. (2002) The health consequences of early soy consumption. J Nutr 132, 559S–65S.PubMedGoogle Scholar
  12. 12.
    Hilakivi-Clarke, L., Onojafe, I., Raygada, M. et al. (1999) Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis. Br J Cancer 80, 1682–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lamartiniere, C.A. (2002) Timing of exposure and mammary cancer risk. J Mammary Gland Biol Neoplasia 7, 67–76.PubMedCrossRefGoogle Scholar
  14. 14.
    Lamartiniere, C.A., Cotroneo, M.S., Fritz, W.A., Wang, J., Mentor-Marcel, R., and Elgavish, A. (2002) Genistein chemoprevention: Timing and mechanisms of action in murine mammary and prostate. J Nutr 132, 552S–8S.PubMedGoogle Scholar
  15. 15.
    Anderson, J.J.B., Anthony, M., Messina, M., and Garner, S.C. (1999) Effects of phyto-oestrogens on tissues. Nutr Res Rev 12, 75–116.PubMedCrossRefGoogle Scholar
  16. 16.
    Allred, C.D., Allred, K.F., Ju, Y.H., Virant, S.M., and Helferich, W.G. (2001) Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res 61, 5045–50.PubMedGoogle Scholar
  17. 17.
    Hsieh, C.Y., Santell, R.C., Haslam, S.Z., and Helferich, W.G. (1998) Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res 58, 3833–8.PubMedGoogle Scholar
  18. 18.
    Ju, Y.H., Allred, C.D., Allred, K.F., Karko, K.L., Doerge, D.R., and Helferich, W.G. (2001) Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr 131, 2957–62.PubMedGoogle Scholar
  19. 19.
    Zava, D.T., and Duwe, G. (1997) Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr Cancer 27, 31–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Mizunuma, H., Kanazawa, K., Ogura, S., Otsuka, S., and Nagai, H. (2002) Anticarcinogenic effects of isoflavones may be mediated by genistein in mouse mammary tumor virus-induced breast cancer. Oncology 62, 78–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Jin, Z., and MacDonald, R.S. (2002) Soy isoflavones increase latency of spontaneous mammary tumors in mice. J Nutr 132, 3186–90.PubMedGoogle Scholar
  22. 22.
    Vantyghem, S.A., Wilson, S.M., Postenka, C.O., Al-Katib, W., Tuck, A.B., and Chambers, A.F. (2005) Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model. Cancer Res 65, 3396–403.PubMedGoogle Scholar
  23. 23.
    Li, D., Yee, J.A., McGuire, M.H., Murphy, P.A., and Yan, L. (1999) Soybean isoflavones reduce experimental metastasis in mice. J Nutr 129, 1075–8.PubMedGoogle Scholar
  24. 24.
    Singh, A.V., Franke, A.A., Blackburn, G.L., and Zhou, J.R. (2006) Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis. Cancer Res 66, 1851–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Raffoul, J.J., Banerjee, S., Che, M. et al. (2007) Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model. Int J Cancer 120, 2491–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Murrill, W.B., Brown, N.M., Zhang, J.X., Manzolillo, P.A., Barnes, S., and Lamartiniere, C.A. (1996) Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 17, 1451–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Russo, J., and Russo, I.H. (1978) DNA labeling index and structure of the rat mammary gland as determinants of its susceptibility to carcinogenesis. J Natl Cancer Inst 61, 1451–9.PubMedGoogle Scholar
  28. 28.
    Russo, J., Moral, R., Balogh, G.A., Mailo, D., and Russo, I.H. (2005) The protective role of pregnancy in breast cancer. Breast Cancer Res 7, 131–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Brown, N.M., Wang, J., Cotroneo, M.S., Zhao, Y.X., and Lamartiniere, C.A. (1998) Prepubertal genistein treatment modulates TGF-alpha, EGF and EGF-receptor mRNAs and proteins in the rat mammary gland. Mol Cell Endocrinol 144, 149–65.PubMedCrossRefGoogle Scholar
  30. 30.
    Dave, B., Eason, R.R., Till, S.R. et al. (2005) The soy isoflavone genistein promotes apoptosis in mammary epithelial cells by inducing the tumor suppressor PTEN. Carcinogenesis 26, 1793–803.PubMedCrossRefGoogle Scholar
  31. 31.
    Cabanes, A., Wang, M., Olivo, S. et al. (2004) Prepubertal estradiol and genistein exposures up-regulate BRCA1 mRNA and reduce mammary tumorigenesis. Carcinogenesis 25, 741–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Rowell, C., Carpenter, D.M., and Lamartiniere, C.A. (2005) Chemoprevention of breast cancer, proteomic discovery of genistein action in the rat mammary gland. J Nutr 135, 2953S–9S.PubMedGoogle Scholar
  33. 33.
    Fotsis, T., Pepper, M.S., Aktas, E. et al. (1997) Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 57, 2916–21.PubMedGoogle Scholar
  34. 34.
    Kyle, E., Neckers, L., Takimoto, C., Curt, G., and Bergan, R. (1997) Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. Mol Pharmacol 51, 193–200.PubMedGoogle Scholar
  35. 35.
    Suzuki, K., Koike, H., Matsui, H. et al. (2002) Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3. Int J Cancer 99, 846–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Okura, A., Arakawa, H., Oka, H., Yoshinari, T., and Monden, Y. (1988) Effect of genistein on topoisomerase activity and on the growth of [Val 12]Ha-ras-transformed NIH 3T3 cells. Biochem Biophys Res Commun 157, 183–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Evans, B.A., Griffiths, K., and Morton, M.S. (1995) Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 147, 295–302.PubMedCrossRefGoogle Scholar
  38. 38.
    Davis, J.N., Kucuk, O., and Sarkar, F.H. (1999) Genistein inhibits NF-kappa B activation in prostate cancer cells. Nutr Cancer 35, 167–74.PubMedCrossRefGoogle Scholar
  39. 39.
    Gong, L., Li, Y., Nedeljkovic-Kurepa, A., and Sarkar, F.H. (2003) Inactivation of NF-kappaB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene 22, 4702–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Fotsis, T., Pepper, M., Adlercreutz, H. et al. (1993) Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 90, 2690–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Li, Y., Che, M., Bhagat, S. et al. (2004) Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia (New York) 6, 354–63.CrossRefGoogle Scholar
  42. 42.
    Pinski, J., Wang, Q., Quek, M.L. et al. (2006) Genistein-induced neuroendocrine differentiation of prostate cancer cells. Prostate 66, 1136–43.PubMedCrossRefGoogle Scholar
  43. 43.
    Pollard, M., and Luckert, P.H. (1997) Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats. Nutr Cancer 28, 41–45.PubMedCrossRefGoogle Scholar
  44. 44.
    Pylkkanen, L., Makela, S., and Santti, R. (1996) Animal models for the preneoplastic lesions of the prostate. Eur Urol 30, 243–8.PubMedGoogle Scholar
  45. 45.
    Zhou, J.R., Gugger, E.T., Tanaka, T., Guo, Y., Blackburn, G.L., and Clinton, S.K. (1999) Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr 129, 1628–35.PubMedGoogle Scholar
  46. 46.
    Wang, J., Eltoum, I.E., and Lamartiniere, C.A. (2002) Dietary genistein suppresses chemically induced prostate cancer in Lobund-Wistar rats. Cancer Lett 186, 11–18.PubMedCrossRefGoogle Scholar
  47. 47.
    Mentor-Marcel, R., Lamartiniere, C.A., Eltoum, I.E., Greenberg, N.M., and Elgavish, A. (2001) Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res 61, 6777–82.PubMedGoogle Scholar
  48. 48.
    Wang, J., Eltoum, I.E., and Lamartiniere, C.A. (2007) Genistein chemoprevention of prostate cancer in TRAMP mice. J Carcinog 6, 3. doi: 10.1186/1477-3163-6-3.PubMedCrossRefGoogle Scholar
  49. 49.
    Dalu, A., Haskell, J.F., Coward, L., and Lamartiniere, C.A. (1998) Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate. Prostate 37, 36–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Fritz, W.A., Wang, J., Eltoum, I.E., and Lamartiniere, C.A. (2002) Dietary genistein down-regulates androgen and estrogen receptor expression in the rat prostate. Mol Cell Endocrinol 186, 89–99.PubMedCrossRefGoogle Scholar
  51. 51.
    Mentor-Marcel, R., Lamartiniere, C.A., Eltoum, I.A., Greenberg, N.M., and Elgavish, A. (2005) Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP). J Nutr 135, 989–95.PubMedGoogle Scholar
  52. 52.
    El Touny, L.H., and Banerjee, P.P. (2007) Akt/GSK3 pathway as a target in genistein-induced inhibition of TRAMP prostate cancer progression towards a poorly differentiated phenotype. Carcinogenesis 28, 1710–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Adlercreutz, H., Honjo, H., Higashi, A. et al. (1991) Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Amer J Clin Nutr 54, 1093–100.PubMedGoogle Scholar
  54. 54.
    Lee, H.P., Gourley, L., Duffy, S.W., Esteve, J., Lee, J., and Day, N.E. (1991) Dietary effects on breast-cancer risk in Singapore. Lancet 337, 1197–200.PubMedCrossRefGoogle Scholar
  55. 55.
    Ziegler, R.G., Hoover, R.N., Pike, M.C. et al. (1993) Migration patterns and breast cancer risk in Asian-American women. J Nat Cancer Inst 85, 1819–27.PubMedCrossRefGoogle Scholar
  56. 56.
    Shu, X.O., Jin, F., Dai, Q. et al. (2001) Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 10, 483–8.PubMedGoogle Scholar
  57. 57.
    Parkin, D.M., Pisani, P., and Ferlay, J. (1999) Global cancer statistics. CA Cancer J Clin 49, 33–64.PubMedCrossRefGoogle Scholar
  58. 58.
    Cook, L.S., Goldoft, M., Schwartz, S.M., and Weiss, N.S. (1999) Incidence of adenocarcinoma of the prostate in Asian immigrants to the United States and their descendants. J Urol 161, 152–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Haenszel, W., and Kurihara, M. (1968) Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J Nat Cancer Inst 40, 43–68.PubMedGoogle Scholar
  60. 60.
    Shimizu, H., Ross, R.K., Bernstein, L., Yatani, R., Henderson, B.E., and Mack, T.M. (1991) Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 63, 963–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Whittemore, A.S., Kolonel, L.N., Wu, A.H. et al. (1995) Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst 87, 652–61.PubMedCrossRefGoogle Scholar
  62. 62.
    Burns, J., Yokota, T., Ashihara, H., Lean, M.E., and Crozier, A. (2002) Plant foods and herbal sources of resveratrol. J Agri Food Chem 50, 3337–40.CrossRefGoogle Scholar
  63. 63.
    Jang, M., Cai, L., Udeani, G.O. et al. (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 218–20.PubMedCrossRefGoogle Scholar
  64. 64.
    Provinciali, M., Re, F., Donnini, A. et al. (2005) Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer 115, 36–45.PubMedCrossRefGoogle Scholar
  65. 65.
    Bhat, K.P., and Pezzuto, J.M. (2002) Cancer chemopreventive activity of resveratrol. Ann N Y Acad Sci 957, 210–29.PubMedCrossRefGoogle Scholar
  66. 66.
    Le Corre, L., Chalabi, N., Delort, L., Bignon, Y.J., and Bernard-Gallon, D.J. (2005) Resveratrol and breast cancer chemoprevention: Molecular mechanisms. Mol Nutr Food Res 49, 462–71.PubMedCrossRefGoogle Scholar
  67. 67.
    Levy-Lahad, E., and Friedman, E. (2007) Cancer risks among BRCA1 and BRCA2 mutation carriers. Br J Cancer 96, 11–15.PubMedCrossRefGoogle Scholar
  68. 68.
    Bhat, K.P., Lantvit, D., Christov, K., Mehta, R.G., Moon, R.C., and Pezzuto, J.M. (2001) Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res 61, 7456–63.PubMedGoogle Scholar
  69. 69.
    Banerjee, S., Bueso-Ramos, C., and Aggarwal, B.B. (2002) Suppression of 7,12-dimethylbenz(a) anthracene-induced mammary carcinogenesis in rats by resveratrol: Role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res 62, 4945–54.PubMedGoogle Scholar
  70. 70.
    Whitsett, T.G., Jr., and Lamartiniere, C.A. (2006) Genistein and resveratrol: Mammary cancer chemoprevention and mechanisms of action in the rat. Expert Rev Anticancer Ther 6, 1699–706.PubMedCrossRefGoogle Scholar
  71. 71.
    Whitsett, T., Carpenter, M., and Lamartiniere, C.A. (2006) Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats. J Carcinog 5, 15. doi: 10.1186/1477-3163-5-15.PubMedCrossRefGoogle Scholar
  72. 72.
    Sato, M., Pei, R.J., Yuri, T., Danbara, N., Nakane, Y., and Tsubura, A. (2003) Prepubertal resveratrol exposure accelerates N-methyl-N-nitrosourea-induced mammary carcinoma in female Sprague-Dawley rats. Cancer Lett 202, 137–45.PubMedCrossRefGoogle Scholar
  73. 73.
    Russo, J., Wilgus, G., and Russo, I.H. (1979) Susceptibility of the mammary gland to carcinogenesis: I Differentiation of the mammary gland as determinant of tumor incidence and type of lesion. Am J Pathol 96, 721–36.PubMedGoogle Scholar
  74. 74.
    Aziz, M.H., Nihal, M., Fu, V.X., Jarrard, D.F., and Ahmad, N. (2006) Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. Mol Cancer Ther 5, 1335–41.PubMedCrossRefGoogle Scholar
  75. 75.
    Kim, Y.A., Rhee, S.H., Park, K.Y., and Choi, Y.H. (2003) Antiproliferative effect of resveratrol in human prostate carcinoma cells. J Med Food 6, 273–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Lin, H.Y., Shih, A., Davis, F.B. et al. (2002) Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line. J Urol 168, 748–55.PubMedCrossRefGoogle Scholar
  77. 77.
    Morris, G.Z., Williams, R.L., Elliott, M.S., and Beebe, S.J. (2002) Resveratrol induces apoptosis in LNCaP cells and requires hydroxyl groups to decrease viability in LNCaP and DU 145 cells. Prostate 52, 319–29.PubMedCrossRefGoogle Scholar
  78. 78.
    Sgambato, A., Ardito, R., Faraglia, B., Boninsegna, A., Wolf, F.I., and Cittadini, A. (2001) Resveratrol, a natural phenolic compound, inhibits cell proliferation and prevents oxidative DNA damage. Mut Res 496, 171–80.CrossRefGoogle Scholar
  79. 79.
    Manna, S.K., Mukhopadhyay, A., and Aggarwal, B.B. (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: Potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 164, 6509–19.PubMedGoogle Scholar
  80. 80.
    Jayatilake, G.S., Jayasuriya, H., Lee, E.S. et al. (1993) Kinase inhibitors from Polygonum cuspidatum. J Nat Prod 56, 1805–10.PubMedCrossRefGoogle Scholar
  81. 81.
    Kimura, Y., Okuda, H., and Arichi, S. (1985) Effects of stilbene derivatives on arachidonate metabolism in leukocytes. Biochim Biophys Acta 837, 209–12.PubMedCrossRefGoogle Scholar
  82. 82.
    Chanvitayapongs, S., Draczynska-Lusiak, B., and Sun, A.Y. (1997) Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Neuroreport 8, 1499–502.PubMedCrossRefGoogle Scholar
  83. 83.
    Mitchell, S.H., Zhu, W., and Young, C.Y. (1999) Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res 59, 5892–5.PubMedGoogle Scholar
  84. 84.
    Hsieh, T.C., and Wu, J.M. (2000) Grape-derived chemopreventive agent resveratrol decreases prostate-specific antigen (PSA) expression in LNCaP cells by an androgen receptor (AR)-independent mechanism. Anticancer Res 20, 225–8.PubMedGoogle Scholar
  85. 85.
    Gao, S., Liu, G.Z., and Wang, Z. (2004) Modulation of androgen receptor-dependent transcription by resveratrol and genistein in prostate cancer cells. Prostate 59, 214–25.PubMedCrossRefGoogle Scholar
  86. 86.
    Harper, C.E., Patel, B.B., Wang, J., Arabshahi, A., Eltoum, I.A., and Lamartiniere, C.A. (2007) Resveratrol suppresses prostate cancer progression in transgenic mice. Carcinogenesis 28, 1946–53.PubMedCrossRefGoogle Scholar
  87. 87.
    Litvinov, I.V., De Marzo, A.M., and Isaacs, J.T. (2003) Is the Achilles' heel for prostate cancer therapy a gain of function in androgen receptor signaling? J Clin Endocrinol Metab 88, 2972–82.PubMedCrossRefGoogle Scholar
  88. 88.
    Litvinov, I.V., Vander Griend, D.J., Antony, L. et al. (2006) Androgen receptor as a licensing factor for DNA replication in androgen-sensitive prostate cancer cells. Proc Natl Acad Sci USA 103, 15085–90.PubMedCrossRefGoogle Scholar
  89. 89.
    Litvinov, I.V., Antony, L., Dalrymple, S.L., Becker, R., Cheng, L., and Isaacs, J.T. (2006) PC3, but not DU145, human prostate cancer cells retain the coregulators required for tumor suppressor ability of androgen receptor. Prostate 66, 1329–38.PubMedCrossRefGoogle Scholar
  90. 90.
    Kopp, P. (1998) Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the ‘French paradox’? Eur J Endocrinol 138, 619–20.PubMedCrossRefGoogle Scholar
  91. 91.
    Renaud, S., and de Lorgeril, M. (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339, 1523–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Sun, A.Y., Simonyi, A., and Sun, G.Y. (2002) The "French Paradox" and beyond: Neuroprotective effects of polyphenols. Free Radic Biol Med 32, 314–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Levi, F., Pasche, C., Lucchini, F., Ghidoni, R., Ferraroni, M., and La Vecchia, C. (2005) Resveratrol and breast cancer risk. Eur J Cancer Prev 14, 139–42.PubMedCrossRefGoogle Scholar
  94. 94.
    Bianchini, F., and Vainio, H. (2003) Wine and resveratrol: Mechanisms of cancer prevention? Eur J Cancer Prev 12, 417–25.PubMedCrossRefGoogle Scholar
  95. 95.
    Hanf, V., and Gonder, U. (2005) Nutrition and primary prevention of breast cancer: Foods, nutrients and breast cancer risk. Eur J Obstet Gynecol Reprod Biol 123, 139–49.PubMedCrossRefGoogle Scholar
  96. 96.
    Singletary, K.W., and Gapstur, S.M. (2001) Alcohol and breast cancer: Review of epidemiologic and experimental evidence and potential mechanisms. JAMA 286, 2143–51.PubMedCrossRefGoogle Scholar
  97. 97.
    Steinberg, J., and Goodwin, P.J. (1991) Alcohol and breast cancer risk – putting the current controversy into perspective. Br Cancer Res Treat 19, 221–31.CrossRefGoogle Scholar
  98. 98.
    Schoonen, W.M., Salinas, C.A., Kiemeney, L.A., and Stanford, J.L. (2005) Alcohol consumption and risk of prostate cancer in middle-aged men. Int J Cancer 113, 133–40.PubMedCrossRefGoogle Scholar
  99. 99.
    Zhou, J.R., Yu, L., Mai, Z., and Blackburn, G.L. (2004) Combined inhibition of estrogen-dependent human breast carcinoma by soy and tea bioactive components in mice. Int J Cancer 108, 8–14.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Timothy G. WhitsettJr
    • 1
  • Leah M. Cook
    • 1
  • Brijesh B. Patel
    • 1
  • Curt E. Harper
    • 1
  • Jun Wang
    • 1
  • Coral A. Lamartiniere
    • 1
    • 2
  1. 1.Department of Pharmacology and ToxicologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.UAB Comprehensive Cancer CenterUniversity of Alabama at BirminghamBirminghamUSA

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