Skip to main content
Log in

Chemoprevention of Prostate Cancer

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Chemoprevention is prevention of cancer by administering natural or synthetic chemicals. Anti-androgens are among the promising chemopreventive agents for prostate cancer because prostate epithelium is androgen dependent. A National Cancer Institute supported large, randomized, clinical prostate cancer chemoprevention trial has been conducted to test the efficacy of finasteride, an inhibitor of 5-α-reductase, which converts testosterone to 5-hydroxy-testosterone. Now the focus is on micronutrients and phytochemicals, which have potential preventive effects against prostate cancer. Lycopene, soy isoflavones, vitamin E and selenium are among the most promising nutritional chemopreventive agents. Another NCI supported large clinical chemoprevention trial was recently started to investigate the efficacy of selenium and vitamin E, alone or in combination in the prevention of prostate cancer. Inclusion of appropriate biomarkers in clinical trials will help elucidate the mechanisms by which genetic and epigenetic pathways of carcinogenesis are modulated by nutrients and phytochemicals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Greenlee RT, Hill-Harmon MB, Murray T, Thun M: Cancer statistics. CA Cancer J Clin 51: 15–36, 2001

    Google Scholar 

  2. Sakr WA, Haas GP, Cassin BJ, Pontes JE, Crissman JD: The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 150: 379–385, 1993

    Google Scholar 

  3. Greenwald P, Lieberman R: Chemoprevention trials for prostate cancer. In: Chung L, Isaacs W, Simons J (eds) Prostate Cancer in the Twenty-First Century, Humana Press Inc, Totowa, NJ 2001, pp 499–518

    Google Scholar 

  4. Kelloff GJ, Lieberman R, Brawer MK, Crawford ED, Miller G: Strategies for chemoprevention of prostate cancer. Prostate Cancer and Prostate Dis 2: 27–33, 1999

    Google Scholar 

  5. Tsai H, Werber J, Davia MO, Edelman M, Tanaka KE, Melman A, Christ GJ, Geliebter J: Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells. Biochem Biophys Res Commun 22: 64–69, 1996

    Google Scholar 

  6. Mehta PP, Lokeshwar BL, Schiller PC, Bendix MV, Ostenson RC, Howard GA, Roos BA: Gap-junctional communication in normal and neoplastic prostate epithelial cells and its regulation by cAMP. Mol Carcinog 15: 18–32, 1996

    Google Scholar 

  7. Mehta P, Perez-Stable C, Nadji M, Mian M, Asotra K, Roos BA: Suppression of human prostate cancer cell growth by forced expression of connexin genes. Develop Gene 24: 91–110, 1999

    Google Scholar 

  8. Mehta PP, Bertram JS, Loewenstein WR: Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44: 187–196, 1986

    Google Scholar 

  9. Hossain MZ, Wilkens LR, Mehta PP, Loewenstein W, Bertram JS: Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10: 1743–1748, 1989

    Google Scholar 

  10. Zhang L-X, Cooney RV, Bertram JS: Carotenoids up-regulate connexin 43 gene expression independent of their pro-vitamin A or antioxidant properties. Cancer Res 52: 5707–5712, 1992

    Google Scholar 

  11. Rogers M, Berestecky JM, Hossain MZ, Guo HM, Kadle R, Nicholson BJ, Bertram JS: Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein. Mol Carcinog 3: 335–343, 1990

    Google Scholar 

  12. Goldberg GS, Bertram JS: Retinoids, gap junctional communication and suppression of epithelial tumors. In Vivo 8: 745–754, 1994

    Google Scholar 

  13. Zhang L-X, Cooney RV, Bertram JS: Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: Relationship to their cancer chemopreventive action. Carcinogenesis 12: 2109–2114, 1991

    Google Scholar 

  14. Bertram JS, Pung A, Churley M, Kappock TJ 4th, Wilkins LR, Cooney RV: Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis 12: 671–678, 1991

    Google Scholar 

  15. Rajah R, Valentinis B, Cohen P: Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta-1 on programmed cell death through a p53-and IGF-independent mechanism. J Biol Chem 272: 12181–12188, 1997

    Google Scholar 

  16. Cohen P, Peehl DM, Rosenfeld RG: The IGF axis in the prostate. Hormone Metab Res 26: 81–84, 1994

    Google Scholar 

  17. Cohen P, Peehl DM, Lamson G, Rosenfeld RG: Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells. J Clin Endocrinol Metab 73: 401–407, 1991

    Google Scholar 

  18. Chan JM, Stampfer MJ, Giovanucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M: Plasma insulin-like growth factor-1 and prostate cancer risk: A prospective study. Science 279: 563–566, 1998

    Google Scholar 

  19. Giovannucci E: Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res 51(Suppl 3): 34–41, 1999

    Google Scholar 

  20. Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO: Insulin-like growth factor-1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer 76: 1115–1118, 1997

    Google Scholar 

  21. Wolk A, Mantzoros CS, Andersson SO, Bergstrom R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D: Insulin-like growth factor-1 and prostate cancer risk: A population-based, case-control study. J Natl Cancer Inst 90: 911–915, 1998

    Google Scholar 

  22. Pollak M, Beamer W, Zhang JC: Insulin-like growth factors and prostate cancer. Cancer Met Rev 17: 383–390, 1998–1999

    Google Scholar 

  23. Sharoni Y, Levy Y, et al. (Personal communication and unpublished observations)

  24. Feigl P, Blumenstein B, Thompson I, Crowley J, Wolf M, Kramer BS, Coltman CA Jr, Brawley OW, Ford LG: Design of the prostate cancer prevention trial (PCPT). Control Clin Trials 16: 150–163, 1995

    Google Scholar 

  25. Cote RJ, Skinner EC, Salem CE, Mertes SJ, Stanczyk FZ, Henderson BE, Pike MC, Ross RK: The effect of finasteride on the prostate gland in men with elevated serum prostate specific antigen (PSA) levels. Brit J Cancer 78: 413–418, 1998

    Google Scholar 

  26. Evans BA, Griffiths K, Morton MS: Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 147(2): 295–302, 1995

    Google Scholar 

  27. Hussain M, Sarkar F, Djuric Z, Pollak M, Banerjee M, Doerge D, Fontana J, Chinni S, Davis J, Forman J, Wood D, Kucuk O: Soy isoflavones in the treatment of prostate cancer. J Nutr 132(3): 575S–576S, 2002

    Google Scholar 

  28. Davis JN, Muqim N, Bhuiyan M, Kucuk O, Pienta KJ, Sarkar FH: Inhibition of prostate specific antigen expression by genistein in prostate cancer cells. Int J Oncol 16: 1091–1097, 2000

    Google Scholar 

  29. Davis JN, Singh B, Bhuiyan M, Sarkar FH: Genistein induced up-regulation of p21, down regulation of cyclin B and induction of apoptosis in prostate cancer cells. Nutr Cancer 32(3): 123–131, 1998

    Google Scholar 

  30. Mentor-Marcel R, Lamartiniere CA, Eltoum IE, Greenberg NM, Elgavish A: Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res 61(18): 6777–6782, 2001

    Google Scholar 

  31. Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, Giovannucci E: Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 90: 1219–1224, 1998

    Google Scholar 

  32. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 276: 1957–1963, 1996

    Google Scholar 

  33. Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbull BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D, Borosso C, Falk S, Rounder J: Decreased incidence of prostate cancer with selenium supplementation: Results of a double-blind cancer prevention trial. Br J Urol 81: 730–734, 1998

    Google Scholar 

  34. Cohen LA (ed): Selenium and cancer: Larry C. Clark memorial issue. Nutr Cancer 40: 1–78, 2001

  35. Chan JM, Stampfer MJ, Ma J, Rimm EB, Willett WC, Giovannucci EL: Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomark Prev 8: 893–899, 1999

    Google Scholar 

  36. Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, Haapakoski J, Malila N, Rautalahti M, Ripatti S, Maenpaa H, Teerenhovi L, Koss L, Virolainen M, Edwards BK: Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial. J Natl Cancer Inst 90: 440–446, 1998

    Google Scholar 

  37. Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group, Heinonen OP, Huttunen JK, Albanes D: The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330: 1029–1035, 1994

    Google Scholar 

  38. Kline K, Yu W, Sanders BG: Vitamin E: Mechanisms of action as tumor cell growth inhibitors. J Nutr 131: 161S–163S, 2001

    Google Scholar 

  39. Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR, Coltman C: SELECT: The next prostate cancer prevention trial. Selenium and Vitamin E Cancer Prevention Trial. J Urol 166: 1311–1315, 2001

    Google Scholar 

  40. Giovannucci E, Clinton SK: Tomatoes, lycopene, and prostate cancer. Proc Soc Exp Biol Med 218: 129–139, 1998

    Google Scholar 

  41. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ: Lower prostate cancer risk in men with elevated plasma lycopene levels: Results of a prospective analysis. Cancer Res 59: 1225–1230, 1999

    Google Scholar 

  42. Giovannucci E: Tomatoes, tomato-based products, lycopene, and cancer: Review of the epidemiologic literature. J Natl Cancer Inst 91: 317–331, 1999

    Google Scholar 

  43. Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC: Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87: 1767–1776, 1995

    Google Scholar 

  44. Kelloff GJ, Lieberman R, Steele VE, Boone CW, Lubet RA, Kopelovitch L, Malone WA, Crowell JA, Sigman CC: Chemoprevention of prostate cancer: Concepts and strategies. Euro Urol 35: 342–350, 1999

    Google Scholar 

  45. Bertram JS: Carotenoids and gene regulation. Nutr Rev 57: 182–191, 1999

    Google Scholar 

  46. Amir H, Karas M, Giat J, Danilenko M, Levy R, Yermiahu T, Levy J, Sharoni Y: Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells. Nutr Cancer 33: 105–112, 1999

    Google Scholar 

  47. Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M, Sharoni Y: Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer 24: 257–266, 1995

    Google Scholar 

  48. Park CK, Ishimi Y, Ohmura M, Yamaguchi M, Ikegami S: Vitamin A and carotenoids stimulate differentiation of mouse osteoblastic cells. J Nutr Sci Vitaminol 43: 281–296, 1997

    Google Scholar 

  49. Karas M, Amir H, Fishman D, Danilenko M, Segal S, Nahum A, Koifmann A, Giat Y, Levy J, Sharoni Y: Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells. Nutr Cancer 36: 101–111, 2000

    Google Scholar 

  50. Kucuk O, Sarkar F, Sakr W, Djuric Z, Khachik F, Pollak M, Bertram J, Grignon D, Banerjee M, Crissman J, Pontes E, Wood DP Jr: Lycopene supplementation in men with localized prostate cancer: Modulation of biomarkers and clinical endpoints. Cancer Epidemiol Biomarkers Prev 10: 861–868, 2001

    Google Scholar 

  51. Chan JM, Stampfer MJ, Giovanucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M: Plasma insulin-like growth factor-1 and prostate cancer risk: A prospective study. Science 279: 563–566, 1998

    Google Scholar 

  52. Nickerson T, Pollak M, Huynh H: Castration-induced apoptosis in the rat ventral prostate is associated with increased expression of genes encoding insulin-like growth factor binding proteins 2,3,4 and 5. Endocrinology 139: 807–810, 1998

    Google Scholar 

  53. Miyake H, Pollak M, Gleave ME: Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models. Cancer Res 60: 3058–3064, 2000

    Google Scholar 

  54. Giovannucci E: Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res 51(Suppl 3): 34–41, 1999

    Google Scholar 

  55. Rajah R, Khare A, Lee PD, Cohen P: Insulin-like growth factor-binding protein-3 is partially responsible for high-serum-induced apoptosis in PC-3 prostate cancer cells. J Endocrinol 163: 487–494, 1999

    Google Scholar 

  56. Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO: Insulin-like growth factor-1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer 76: 1115–1118, 1997

    Google Scholar 

  57. Wolk A, Mantzoros CS, Andersson SO, Bergstrom R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D: Insulin-like growth factor-1 and prostate cancer risk: A population-based, case-control study. J Natl Cancer Inst 90: 911–915, 1998

    Google Scholar 

  58. Pollak M, Beamer W, Zhang JC: Insulin-like growth factors and prostate cancer. Cancer Met Rev 17: 383–390, 1998–1999

    Google Scholar 

  59. Rajah R, Valentinis B, Cohen P: Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta-1 on programmed cell death through a p53-and IGF-independent mechanism. J Biol Chem 272: 12181–12188, 1997

    Google Scholar 

  60. Matsushima-Nishiwaki R, Shidoji Y, Nishiwaki S, Yamada T, Moriwaki H, Muto Y: Suppression by carotenoids of microcystin-induced morphological changes in mouse hepatocytes. Lipids 30: 1029–1034, 1995

    Google Scholar 

  61. Zhang L-X, Cooney RV, Bertram JS: Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: Relationship to their cancer chemopreventive action. Carcinogenesis 12: 2109–2114, 1991

    Google Scholar 

  62. Bertram JS, Pung A, Churley M, Kappock TJ 4th, Wilkins LR, Cooney RV: Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis 12: 671–678, 1991

    Google Scholar 

  63. Zhang L-X, Cooney RV, Bertram JS: Carotenoids up-regulate connexin43 gene expression independent of their pro-vitamin A or antioxidant properties. Cancer Res 52: 5707–5712, 1992

    Google Scholar 

  64. Hotz-Wagenblatt A, Shalloway D: Gap junctional communication and neoplastic transformation. Crit Rev Oncogenesis 4: 541–558, 1993

    Google Scholar 

  65. Bertram JS, Bortkiewicz H: Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells. Am J Clin Nutr 62(Suppl 6): 1327S–1336S, 1995

    Google Scholar 

  66. Hossain MZ, Wilkens LR, Mehta PP, Loewenstein W, Bertram JS: Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10: 1743–1748, 1989

    Google Scholar 

  67. Mehta PP, Bertram JS, Loewenstein WR: The actions of retinoids on cellular growth correlate with their actions on gap junctional communication. Cell Biol 108: 1053–1065, 1989

    Google Scholar 

  68. Beyer EC, Paul DL, Goodenough DA: Connexin43: A protein from rat heart homologous to a gap junction protein from liver. J Cell Biol 105: 2621–2629, 1987

    Google Scholar 

  69. Mehta PP, Bertram JS, Loewenstein WR: Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44: 187–196, 1986

    Google Scholar 

  70. Loewenstein WR: Junctional intercellular communication and the control of growth. Biochem Biophys Acta 560: 1–65, 1979

    Google Scholar 

  71. Yamasaki H: Gap junctional intercellular communication and carcinogenesis. Carcinogenesis 11: 1051–1058, 1990

    Google Scholar 

  72. Chen S-C, Pelletier DB, Peng A, Boynton AL: Connexin43 reverses the phenotype of transformed cells and alters their expression of cyclin/cyclin-dependent kinases. Cell Growth Diff 6: 681–690, 1995

    Google Scholar 

  73. Gius D, Botero A, Shah S, Curry HA: Intracellular oxidation/reduction status in the regulation of transcription factors NF-kappaB and AP-1. Toxicol Lett 106: 93–106, 1999

    Google Scholar 

  74. Riso P, Pinder A, Santangelo A, Porrini M: Does tomato consumption effectively increase the resistance of lymphocyte DNA to oxidative damage? Am J Clin Nutr 69: 712–718, 1999

    Google Scholar 

  75. Rao AV, Fleshner N, Agarwal S: Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: A case-control study. Nutr Cancer 33: 159–164, 1999

    Google Scholar 

  76. Jewell C, O'Brien NM: Effect of dietary supplementation with carotenoids on xenobiotic metabolizing enzymes in the liver, lung, kidney and small intestine of the rat. Br J Nutr 81: 235–242, 1999

    Google Scholar 

  77. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC: A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 94: 391–398, 2002

    Google Scholar 

  78. Hotz-Wagenblatt A, Shalloway D: Gap junctional communication and neoplastic transformation. Crit Rev Oncogenesis 4: 541–558, 1993

    Google Scholar 

  79. Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, van Breemen R, Ashton D, Bowen PE: Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J Natl Cancer Inst 93: 1872–1879, 2001

    Google Scholar 

  80. Kucuk O, Sarkar F, Sakr W, Djuric Z, Khachik F, Pollak M, Khachik F, Li YW, Banerjee M, Grignon D, Bertram JS, Crissman JD, Pontes EJ, Wood DP Jr: Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 10: 861–868, 2001

    Google Scholar 

  81. Sharoni Y, Levy Y, et al. (Personal communication and unpublished observations)

  82. Rao AV, Agarwal S: Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutr Cancer 31(3): 199–203, 1998

    Google Scholar 

  83. Wang TT, Sathyamoorthy N, Phang JM: Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis 17: 271–275, 1996

    Google Scholar 

  84. Cassidy A, Bingham S, Setchell KD: Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr 60: 333–340, 1994

    Google Scholar 

  85. Schwartz JA, Liu G, Brooks SC: Genistein-mediated attenuation of tamoxifen-induced antagonism from estrogen receptor-regulated genes. Biochem Biophys Res Commun 253: 38–43, 1998

    Google Scholar 

  86. Shen F, Xue X, Weber G: Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells. Anticancer Res 19: 1657–1662, 1999

    Google Scholar 

  87. Tham DM, Gardner CD, Haskell WL: Clinical review 97: Potential health benefits of dietary phytoestrogens: A review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 83(7): 2223–2235, 1998

    Google Scholar 

  88. Anderson JJ, Anthony MS, Cline JM, Washburn SA, Garner SC: Health potential of soy isoflavones for menopausal women. Public Health Nutr 2(4): 489–504, 1999

    Google Scholar 

  89. Giovanucci E: Epidemiological characteristics of prostate cancer. Cancer 75(Suppl): 1766–1777, 1995

    Google Scholar 

  90. Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM: Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 63: 963–966, 1991

    Google Scholar 

  91. Mills PK, Beeson WL, Phillips RL, Fraser GE: Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64: 598–604, 1989

    Google Scholar 

  92. Rose DP, Boyar AP, Wynder EL: International comparison of mortality rates for cancer of the breast, ovary, prostate and colon, and per capita food consumption. Cancer 58: 2363–2371, 1986

    Google Scholar 

  93. Adlercreutz H: Phytoestrogens: Epidemiology and a possible role in cancer prevention. Environ Health Perspect 103(Suppl 7): 103–112, 1995

    Google Scholar 

  94. Adlercreutz H, Fotsis T, Lampe J, Wahala K, Makela T, Brunow G, Hase T: Quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography-mass spectrometry. Scand J Clin Lab Invest 53(Suppl 215): 5–18, 1993

    Google Scholar 

  95. Adlercreutz H, Fotsis T, Bannwart C, Wahala K, Brunow G, Hase T: Isotope dilution gas chromatographic-mass spectrometric identification of genistein. Clinica Chimica Acta 199: 263–278, 1991

    Google Scholar 

  96. Adlercreutz H, Fotsis T, Kurzer MS, Wahala K, Makela T, Hase T: Isotope dilution gas chromatographic-mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces with preliminary results in omnivorous and vegetarian women. Anal Biochem 225: 101–108, 1995

    Google Scholar 

  97. Finlay EMH, Wilson DW, Adlercreutz H, Griffiths K: The identification and measurement of phyto-estrogens in human saliva, plasma, breast aspirate or cyst fluid, and prostatic fluid using gas chromatography-mass spectrometry. J Endocrinol 129(Suppl): 49, 1991

    Google Scholar 

  98. Setchell KDR, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT, et al.: Bioavailability of pure isoflavones in healthy adults and analysis of commercial soy isoflavone supplements. J Nutr 131(Suppl): 1362S–1375S, 2001

    Google Scholar 

  99. Knight DC, Eden JA: A review of the clinical effects of phytoestrogens. Obstet Gynecol 87(5): 897–904, 1996

    Google Scholar 

  100. Wei H, Cai Q, Rahn RO: Inhibition of UV light-and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein. Carcinogenesis 17: 73–77, 1996

    Google Scholar 

  101. Giles D, Wei H: Effect of structurally related flavones/isoflavones on hydrogen peroxide production and oxidative DNA damage in phorbol ester-stimulated HL-60 cells. Nutr Cancer 29: 77–82, 1997

    Google Scholar 

  102. Shao Z, Alpaugh M, Fontana J, Barsky S: Genistein inhibits proliferation similarly in estrogen receptor-positive and negative breast carcinoma cell lines characterized by p21WAF1 induction, G2/M arrest and apoptosis. J Cell Biochem 69: 44–54, 1998

    Google Scholar 

  103. Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L: Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 90: 2690–2694, 1993

    Google Scholar 

  104. Wong CK, Keung WM: Bovine adrenal 3beta-hydroxysteroid dehydrogenase (E.C. 1.1.1._145)/5-ene-4-ene isomerase (E.C. 5.3.3.1): characterization and its inhibition by isoflavones. J Steroid Biochem Mol Biol 71(5–6): 191–202, 1999

    Google Scholar 

  105. Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, et al.: Genistein, a specific inhibitor of tyrosine-specific protein kinase. J Biol Chem 262: 5592–5595, 1987

    Google Scholar 

  106. Okura A, Arakawa H, Oka H, Yoshinari T, Monden Y: Effect of genistein on topoisomerase activity and on the growth of [val 12] Ha-ras transformed NIH 3T3 cells. Biochem Biophys Res Comm 57: 183–189, 1998

    Google Scholar 

  107. Axelsson L, Hellberg C, Melander F, Smith D, Zheng L, Andersson T: Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase. Exp Cell Res 256(1): 257–263, 2000

    Google Scholar 

  108. Davis JN, Singh B, Bhuiyan M, Sarkar FH: Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells. Nutr Cancer 32: 123–131, 1998

    Google Scholar 

  109. Davis JN, Kucuk O, Sarkar FH: Genistein inhibits NF-kappaB activation in prostate cancer cells. Nutr Cancer 35: 167–174, 1999

    Google Scholar 

  110. Davis JN, Kucuk O, Djuric Z, Sarkar FH: Soy isoflavone supplementation in healthy men prevents NF-kappaB activation by TNF-alpha in blood lymphocytes. Free Rad Biol Med 30(11): 1293–1302, 2001

    Google Scholar 

  111. Hussain M, Sarkar F, Djuric Z, Pollak M, Banerjee M, Doerge D, Fontana J, Chinni S, Davis J, Forman J, Wood D, Kucuk O: Soy isoflavones in the treatment of prostate cancer. J Nutr 132(3): 575S–576S, 2002

    Google Scholar 

  112. Davis JN, Muqim N, Bhuiyan M, Kucuk O, Pienta KJ, Sarkar FH: Inhibition of prostate specific antigen expression by genistein in prostate cancer cells. Int J Oncol 16: 1091–1097, 2000

    Google Scholar 

  113. Chan JM, Stampfer MJ, Giovanucci E, Gann PH, Ma J, Wilkinson P, et al.: Plasma insulin-like growth factor-1 and prostate cancer risk: A prospective study. Science 279: 563–566, 1998

    Google Scholar 

  114. Cohen P, Peehl DM, Rosenfeld RG: The IGF axis in the prostate. Hormone Metab Res 26: 81–84, 1994

    Google Scholar 

  115. Cohen P, Peehl DM, Lamson G, Rosenfeld RG: Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells. J Clin Endocrinol Metab 73: 401–407, 1991

    Google Scholar 

  116. Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: Biological actions. Endocr Rev 16: 3–34, 1995

    Google Scholar 

  117. Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, et al.: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: Relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 78: 744–752, 1994

    Google Scholar 

  118. Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, et al.: Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: The relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 80: 2534–2542, 1995

    Google Scholar 

  119. Pollak M, Costantino J, Polychronakos C, Blauer SA, Guyda H, Redmond C, et al.: Effect of tamoxifen on serum insulin-like growth factor I levels in stage I breast cancer patients. J Natl Cancer Inst 82: 1693–1697, 1990

    Google Scholar 

  120. Huynh H, Yang X, Pollak M: Estradiol and antiestrogens regulate a growth inhibitory insulin-like growth factor binding protein 3 autocrine loop in human breast cancer cells. J Biol Chem 271: 1016–1021, 1996

    Google Scholar 

  121. Huynh H, Yang X, Pollak M: A role for insulin-like growth factor binding protein 5 in the antiproliferative action of the antiestrogen ICI 182780. Cell Growth Differ 7: 1501–1506, 1996

    Google Scholar 

  122. Kapiotis S, Hermann M, Held I, Seelos C, Ehringer H, Gmeiner BM: Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arteriosclerosis, Thrombosis Vascular Biol 17: 2868–2874, 1997

    Google Scholar 

  123. Tikkanen MJ, Wahala K, Ojala S, Vihma V, Adlercreutz H: Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proc Natl Acad Sci USA 95: 3106–3110, 1998

    Google Scholar 

  124. Ruiz-Larrea MB, Mohan AR, Paganga G, Miller NJ, Bolwell GP, Rice-Evans CA: Antioxidant activity of phytoestrogenic isoflavones. Free Radical Research 26: 63–70, 1997

    Google Scholar 

  125. Cai Q, Wei H: Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice. Nutr Cancer 25: 1–7, 1996

    Google Scholar 

  126. Djuric Z, Chen G, Doerge D, Heilbrun L, Kucuk O: Effect of soy isoflavone supplementation on oxidative stress in men and women. Cancer Lett 172: 1–6, 2001

    Google Scholar 

  127. Ghosh J, Myers CE: Arachidonic acid stimulates prostate cancer cell growth: Critical role of 5-lipoxygenase. Biochem Biophys Res Commun 235: 418–423, 1997

    Google Scholar 

  128. Hayes RB, Ziegler RG, Gridley G, Swanson C, Greenberg RS, Swanson GM, Schoenberg JB, Silverman DT, Brown LM, Pottern LM, Liff J, Schwartz AG, Fraumeni JF Jr, Hoover RN: Dietary factors and risks for prostate cancer among blacks and whites in the United States. Cancer Epidemiol Biomarkers Prev 8: 25–34, 1999

    Google Scholar 

  129. Ghosh J, Myers CE: Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc Natl Acad Sci USA 95: 13182–13187, 1998

    Google Scholar 

  130. Myers CE, Ghosh J: Lipoxygenase inhibition in prostate cancer. Eur Urol 35: 395–398, 1999

    Google Scholar 

  131. Mori TA, Puddey IB, Burke V, Croft KD, Dunstan DW, Rivera JH, Beilin LJ: Effect of Omega-3 fatty acids on oxidative stress in humans: GC-MS measurement of urinary F2-isoprostane excretion. Redox Rep 5: 45–46, 2000

    Google Scholar 

  132. Norrish AE, Skeaff CM, Arribas GL, Sharpe SJ, Jackson RT: Prostate cancer risk and consumption of fish oils: A dietary biomarker-based case-control study. Br J Cancer 81: 1238–1242, 1999

    Google Scholar 

  133. DiPaola RS, Zhang H, Lambert GH, Meeker R, Licitra E, Rafi MM, Zhu BT, Spaulding H, Goodin S, Toledano MB, Hait WN, Gallo MA: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 339: 785–791, 1998

    Google Scholar 

  134. Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbull BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D, Borosso C, Falk S, Rounder J: Decreased incidence of prostate cancer with selenium supplementation: Results of a double-blind cancer prevention trial. Br J Urol 81(5): 730–734, 1998

    Google Scholar 

  135. Pastori M, Pfander H, Boscoboinik D, Azzi A: Lycopene in association with alpha-tocopherol inhibits at physiological concentration proliferation of prostate carcinoma cells. Biochem Biophys Res Commun 250(3): 582–585, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kucuk, O. Chemoprevention of Prostate Cancer. Cancer Metastasis Rev 21, 111–124 (2002). https://doi.org/10.1023/A:1020809806121

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020809806121

Navigation