Diet and prostate cancer: mechanisms of action and implications for chemoprevention

Abstract

As one of the most prevalent cancers, prostate cancer has enormous public health significance and prevention strategies would attenuate its economic, emotional, physical and social impact. Until recently, however, we have had only modest information about risk factors for this disease, apart from the well-established characteristics of age, family history and place of birth. The large worldwide variation in the incidence of prostate cancer and the increased risk in migrants who move from low-risk to high-risk countries provide strong support for modifiable environmental factors, particularly diet, in its etiology. Thus, dietary agents have gained considerable attention as chemopreventive agents against prostate cancer. Dietary fat, red and processed meat, vitamin E, selenium, tomatoes, cruciforms and green tea have all been linked with the development and aggressiveness of prostate cancer, through a range of molecular mechanisms. The direction of future clinical trials lies in clarifying the effects of these agents and exploring the biological mechanisms responsible for the prevention of prostate cancer. However, owing to the short time period between diagnosis and treatment, conventional dietary intervention techniques are not always realistic. Until large randomized trials confirm the benefit of chemopreventive and dietary modifications, patients can be advised to pursue a diet and lifestyle that enhances overall health.

Key Points

  • Diet is a major contributory factor in the development and progression of prostate cancer, via multiple molecular pathways

  • Fats, red and processed meat, vitamin E, selenium, tomatoes, cruciforms, and green tea are all associated with modification of prostate cancer risk

  • Agents that are associated with reduced risk of prostate cancer potentially share common molecular pathways of action

  • Not all agents that reduce prostate cancer risk in population-based and preclinical studies have shown benefit in clinical trials for prostate cancer prevention

  • As substantial interaction exists between the mechanisms of action of various dietary agents, combination therapy with multiple molecularly targeted agents is likely to be more beneficial than monotherapy

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Figure 1: Androgen receptor and insulin-like growth factor signaling in chemoprevention.
Figure 2: Molecular events in the pathogenesis of prostate cancer.
Figure 3: Signaling pathways altered in response to oxidative stress.

References

  1. 1

    Jemal, A. et al. Cancer statistics, 2008. CA Cancer J. Clin. 58, 71–96 (2008).

  2. 2

    Dhom, G. Epidemiologic aspects of latent and clinically manifest carcinoma of the prostate. J. Cancer Res. Clin. Oncol. 106, 210–218 (1983).

  3. 3

    Marrett, L. D., De, P., Airia, P. & Dryer, D. Cancer in Canada in 2008. CMAJ 179, 1163–1170 (2008).

  4. 4

    Sanda, M. G. et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N. Engl. J. Med. 358, 1250–1261 (2008).

  5. 5

    Chan, J. M. et al. Diet after diagnosis and the risk of prostate cancer progression, recurrence, and death (United States). Cancer Causes Control 17, 199–208 (2006).

  6. 6

    Hsing, A. W., Tsao, L. & Devesa, S. S. International trends and patterns of prostate cancer incidence and mortality. Int. J. Cancer 85, 60–67 (2000).

  7. 7

    Parker, S. L., Tong, T., Bolden, S. & Wingo, P. A. Cancer statistics, 1997. CA Cancer J. Clin. 47, 5–27 (1997).

  8. 8

    Fleshner, N. E. & Fair, W. R. Impact of the environment on urological cancers. AUA Update Series 15, 261–266 (1996).

  9. 9

    Fair, W. R., Fleshner, N. E. & Heston, W. Cancer of the prostate: a nutritional disease? Urology 50, 840–848 (1997).

  10. 10

    Fleshner, N. E. & Fair, W. R. Indications for transition zone biopsy in the detection of prostatic carcinoma. J. Urol. 157, 556–558 (1997).

  11. 11

    Haenszel, W. & Kurihara, M. Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J. Natl Cancer Inst. 40, 43–68 (1968).

  12. 12

    Armstrong, B. & Doll, R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int. J. Cancer 15, 617–631 (1975).

  13. 13

    Mononen, N. & Schleutker, J. Polymorphisms in genes involved in androgen pathways as risk factors for prostate cancer. J. Urol. 181, 1541–1549 (2009).

  14. 14

    Odedina, F. T. et al. Prostate cancer disparities in black men of African descent: a comparative literature review of prostate cancer burden among black men in the United States, Caribbean, United Kingdom, and West Africa. Infect. Agent. Cancer 4 (Suppl. 1), S2 (2009).

  15. 15

    Patel, A. R. & Klein, E. A. Risk factors for prostate cancer. Nat. Clin. Pract. Urol. 6, 87–95 (2009).

  16. 16

    Chan, J. M., Gann, P. H. & Giovannucci, E. L. Role of diet in prostate cancer development and progression. J. Clin. Oncol. 23, 8152–8160 (2005).

  17. 17

    Giovannucci, E. et al. A prospective study of dietary fat and risk of prostate cancer. J. Natl Cancer Inst. 85, 1571–1579 (1993).

  18. 18

    Kolonel, L. N., Nomura, A. M. & Cooney, R. V. Dietary fat and prostate cancer: current status. J. Natl Cancer Inst. 91, 414–428 (1999).

  19. 19

    Platz, E. A., Leitzmann, M. F., Michaud, D. S., Willett, W. C. & Giovannucci, E. Interrelation of energy intake, body size, and physical activity with prostate cancer in a large prospective cohort study. Cancer Res. 63, 8542–8548 (2003).

  20. 20

    Willis, M. S. & Wians, F. H. The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances. Clin. Chim. Acta 330, 57–83 (2003).

  21. 21

    Arber, N. et al. Celecoxib for the prevention of colorectal adenomatous polyps. N. Engl. J. Med. 355, 885–895 (2006).

  22. 22

    Baron, J. A. et al. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 131, 1674–1682 (2006).

  23. 23

    Bertagnolli, M. M. et al. Celecoxib for the prevention of sporadic colorectal adenomas. N. Engl. J. Med. 355, 873–884 (2006).

  24. 24

    Fisher, B. et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl Cancer Inst. 90, 1371–1388 (1998).

  25. 25

    Vogel, V. G. et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295, 2727–2741 (2006).

  26. 26

    Thompson, I. M. et al. The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 349, 215–224 (2003).

  27. 27

    William, W. N. Jr, Heymach, J. V., Kim, E. S. & Lippman, S. M. Molecular targets for cancer chemoprevention. Nat. Rev. Drug Discov. 8, 213–225 (2009).

  28. 28

    Lippman, S. M. & Hong, W. K. Cancer prevention science and practice. Cancer Res. 62, 5119–5125 (2002).

  29. 29

    Astorg, P. Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence. Cancer Causes Control 15, 367–386 (2004).

  30. 30

    Demark-Wahnefried, W. & Moyad, M. A. Dietary intervention in the management of prostate cancer. Curr. Opin. Urol. 17, 168–174 (2007).

  31. 31

    Greenwald, P. Clinical trials in cancer prevention: current results and perspectives for the future. J. Nutr. 134 (12 Suppl.), 3507S–3512S (2004).

  32. 32

    Freedland, S. J. & Aronson, W. J. Obesity and prostate cancer. Urology 65, 433–439 (2005).

  33. 33

    Giovannucci, E., Liu, Y., Platz, E. A., Stampfer, M. J. & Willett, W. C. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int. J. Cancer 121, 1571–1578 (2007).

  34. 34

    Kim, D. J. et al. Premorbid diet in relation to survival from prostate cancer (Canada). Cancer Causes Control 11, 65–77 (2000).

  35. 35

    Rodriguez, C. et al. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol. Biomarkers Prev. 16, 63–69 (2007).

  36. 36

    Hill, P., Wynder, E. L., Garbaczewski, L., Garnes, H. & Walker, A. R. Diet and urinary steroids in black and white North American men and black South African men. Cancer Res. 39, 5101–5105 (1979).

  37. 37

    Fleshner, N. & Zlotta, A. R. Prostate cancer prevention: past, present, and future. Cancer 110, 1889–1899 (2007).

  38. 38

    Hamalainen, E., Adlercreutz, H., Puska, P. & Pietinen, P. Diet and serum sex hormones in healthy men. J. Steroid Biochem. 20, 459–464 (1984).

  39. 39

    Hamalainen, E. K., Adlercreutz, H., Puska, P. & Pietinen, P. Decrease of serum total and free testosterone during a low-fat high-fibre diet. J. Steroid Biochem. 18, 369–370 (1983).

  40. 40

    Rosenthal, M. B. et al. Effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet on levels of serum lipids and estradiol. Am. J. Med. 78, 23–27 (1985).

  41. 41

    Rao, A. V., 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).

  42. 42

    Ngo, T. H., Barnard, R. J., Tymchuk, C. N., Cohen, P. & Aronson, W. J. Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States). Cancer Causes Control 13, 929–935 (2002).

  43. 43

    Ngo, T. H. et al. Effect of isocaloric low-fat diet on human LAPC-4 prostate cancer xenografts in severe combined immunodeficient mice and the insulin-like growth factor axis. Clin. Cancer Res. 9, 2734–2743 (2003).

  44. 44

    Ngo, T. H. et al. Effect of isocaloric low-fat diet on prostate cancer xenograft progression to androgen independence. Cancer Res. 64, 1252–1254 (2004).

  45. 45

    Freedland, S. J. et al. Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. Prostate 68, 11–19 (2008).

  46. 46

    Lloyd, J. C. et al. Effect of isocaloric low fat diet on prostate cancer xenograft progression in a hormone deprivation model. J. Urol. 183, 1619–1624 (2010).

  47. 47

    Wang, Y. et al. Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. J. Natl Cancer Inst. 87, 1456–1462 (1995).

  48. 48

    Kobayashi, N. et al. Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2. Clin. Cancer Res. 12, 4662–4670 (2006).

  49. 49

    Gupta, S. et al. Lipoxygenase-5 is overexpressed in prostate adenocarcinoma. Cancer 91, 737–743 (2001).

  50. 50

    Berquin, I. M. et al. Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J. Clin. Invest. 117, 1866–1875 (2007).

  51. 51

    Berquin, I. M., Edwards, I. J. & Chen, Y. Q. Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett. 269, 363–377 (2008).

  52. 52

    Aronson, W. J. et al. Growth inhibitory effect of low fat diet on prostate cancer cells: results of a prospective, randomized dietary intervention trial in men with prostate cancer. J. Urol. 183, 345–350 (2010).

  53. 53

    Kobayashi, N. et al. Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model. Cancer Res. 68, 3066–3073 (2008).

  54. 54

    Dagnelie, P. C., Schuurman, A. G., Goldbohm, R. A. & van den Brandt, P. A. Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies. BJU Int. 93, 1139–1150 (2004).

  55. 55

    Sinha, R. et al. Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States. Am. J. Epidemiol. 170, 1165–1177 (2009).

  56. 56

    Kazerouni, N., Sinha, R., Hsu, C. H., Greenberg, A. & Rothman, N. Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study. Food Chem. Toxicol. 39, 423–436 (2001).

  57. 57

    Sinha, R. et al. Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings. Food Chem. Toxicol. 36, 279–287 (1998).

  58. 58

    Sinha, R. et al. Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness. Food Chem. Toxicol. 36, 289–297 (1998).

  59. 59

    Cross, A. J. et al. Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study. Int. J. Cancer 118, 3147–3152 (2006).

  60. 60

    Lewin, M. H. et al. Red meat enhances the colonic formation of the DNA adduct O6-carboxymethyl guanine: implications for colorectal cancer risk. Cancer Res. 66, 1859–1865 (2006).

  61. 61

    Tappel, A. Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases. Med. Hypotheses 68, 562–564 (2007).

  62. 62

    Lijinsky, W. N-Nitroso compounds in the diet. Mutat. Res. 443, 129–138 (1999).

  63. 63

    Cross, A. J. & Sinha, R. Meat-related mutagens/carcinogens in the etiology of colorectal cancer. Environ. Mol. Mutagen. 44, 44–55 (2004).

  64. 64

    Sinha, R. et al. Development of a food frequency questionnaire module and databases for compounds in cooked and processed meats. Mol. Nutr. Food Res. 49, 648–655 (2005).

  65. 65

    Bingham, S. A., Hughes, R. & Cross, A. J. Effect of white versus red meat on endogenous N-nitrosation in the human colon and further evidence of a dose response. J. Nutr. 132 (11 Suppl.), 3522S–3525S (2002).

  66. 66

    Cross, A. J., Pollock, J. R. & Bingham, S. A. Red meat and colorectal cancer risk: the effect of dietary iron and haem on endogenous N-nitrosation. IARC Sci. Publ. 156, 205–206 (2002).

  67. 67

    Cross, A. J., Pollock, J. R. & Bingham, S. A. Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Res. 63, 2358–2360 (2003).

  68. 68

    Kolonel, L. N. Fat, meat, and prostate cancer. Epidemiol. Rev. 23, 72–81 (2001).

  69. 69

    Park, S. Y., Murphy, S. P., Wilkens, L. R., Henderson, B. E. & Kolonel, L. N. Fat and meat intake and prostate cancer risk: the multiethnic cohort study. Int. J. Cancer 121, 1339–1345 (2007).

  70. 70

    Ni, J. & Yeh, S. The roles of alpha-vitamin E and its analogues in prostate cancer. Vitam. Horm. 76, 493–518 (2007).

  71. 71

    el Attar, T. M. & Lin, H. S. Effect of vitamin C and vitamin E on prostaglandin synthesis by fibroblasts and squamous carcinoma cells. Prostaglandins Leukot. Essent. Fatty Acids 47, 253–257 (1992).

  72. 72

    [No authors listed] The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N. Engl. J. Med. 330, 1029–1035 (1994).

  73. 73

    Beier, R. et al. Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events. EMBO J. 19, 5813–5823 (2000).

  74. 74

    Gunawardena, K., Murray, D. K. & Meikle, A. W. Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis. Prostate 44, 287–295 (2000).

  75. 75

    Israel, K., Yu, W., Sanders, B. G. & Kline, K. Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis. Nutr. Cancer 36, 90–100 (2000).

  76. 76

    Ni, J. et al. Vitamin E succinate inhibits human prostate cancer cell growth via modulating cell cycle regulatory machinery. Biochem. Biophys. Res. Commun. 300, 357–363 (2003).

  77. 77

    Venkateswaran, V., Fleshner, N. E. & Klotz, L. H. Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines. J. Urol. 168, 1578–1582 (2002).

  78. 78

    Venkateswaran, V., Fleshner, N. E. & Klotz, L. H. Synergistic effect of vitamin E and selenium in human prostate cancer cell lines. Prostate Cancer Prostatic Dis. 7, 54–56 (2004).

  79. 79

    Zhang, Y. et al. Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. Proc. Natl Acad. Sci. USA 99, 7408–7413 (2002).

  80. 80

    Jiang, Q., Wong, J., Fyrst, H., Saba, J. D. & Ames, B. N. gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. Proc. Natl Acad. Sci. USA 101, 17825–17830 (2004).

  81. 81

    Ni, J. et al. Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway. Cancer Res. 65, 9807–9816 (2005).

  82. 82

    Syed, D. N., Suh, Y., Afaq, F. & Mukhtar, H. Dietary agents for chemoprevention of prostate cancer. Cancer Lett. 265, 167–176 (2008).

  83. 83

    Fleshner, N., Fair, W. R., Huryk, R. & Heston, W. D. Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice. J. Urol. 161, 1651–1654 (1999).

  84. 84

    Venkateswaran, V. et al. A combination of micronutrients is beneficial in reducing the incidence of prostate cancer and increasing survival in the Lady transgenic model. Cancer Prev. Res. (Phila. PA) 2, 473–483 (2009).

  85. 85

    Lippman, S. M. et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301, 39–51 (2009).

  86. 86

    Combs, G. F. Jr. Chemopreventive mechanisms of selenium. Med. Klin. 94 (Suppl. 3), 18–24 (1999).

  87. 87

    Helzlsouer, K. J. et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J. Natl Cancer Inst. 92, 2018–2023 (2000).

  88. 88

    Yoshizawa, K. et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J. Natl Cancer Inst. 90, 1219–1224 (1998).

  89. 89

    Li, H. et al. A prospective study of plasma selenium levels and prostate cancer risk. J. Natl Cancer Inst. 96, 696–703 (2004).

  90. 90

    Duffield-Lillico, A. J. et al. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int. 91, 608–612 (2003).

  91. 91

    Dong, Y. et al. Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling. Cancer Res. 64, 19–22 (2004).

  92. 92

    Morris, J. D. et al. Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity. Cancer Lett. 239, 111–122 (2006).

  93. 93

    Venkateswaran, V., Klotz, L. H. & Fleshner, N. E. Selenium modulation of cell proliferation and cell cycle biomarkers in human prostate carcinoma cell lines. Cancer Res. 62, 2540–2545 (2002).

  94. 94

    Venkateswaran, V. Selenium and prostate cancer: biological pathways and biochemical nuances. Cancer Ther. 4, 73–80 (2006).

  95. 95

    Zhong, W. & Oberley, T. D. Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer Res. 61, 7071–7078 (2001).

  96. 96

    Husbeck, B., Nonn, L., Peehl, D. M. & Knox, S. J. Tumor-selective killing by selenite in patient-matched pairs of normal and malignant prostate cells. Prostate 66, 218–225 (2006).

  97. 97

    D'Andrea, G. M. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J. Clin. 55, 319–321 (2005).

  98. 98

    Tabassum A., Bristow, R. G. & Venkateswaran, V. Ingestion of selenium and other antioxidants during prostate cancer radiotherapy: a good thing? Cancer Treat. Rev. 36, 230–234 (2010).

  99. 99

    Hu, H., Jiang, C., Ip, C., Rustum, Y. M. & Lu, J. Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells. Clin. Cancer Res. 11, 2379–2388 (2005).

  100. 100

    Jiang, C., Wang, Z., Ganther, H. & Lu, J. Distinct effects of methylseleninic acid versus selenite on apoptosis, cell cycle, and protein kinase pathways in DU145 human prostate cancer cells. Mol. Cancer Ther. 1, 1059–1066 (2002).

  101. 101

    Jiang, C., Hu, H., Malewicz, B., Wang, Z. & Lu, J. Selenite-induced p53 Ser-15 phosphorylation and caspase-mediated apoptosis in LNCaP human prostate cancer cells. Mol. Cancer Ther. 3, 877–884 (2004).

  102. 102

    Yamaguchi, K. et al. Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Oncogene 24, 5868–5877 (2005).

  103. 103

    Wu, Y., Zu, K., Warren, M. A., Wallace, P. K. & Ip, C. Delineating the mechanism by which selenium deactivates Akt in prostate cancer cells. Mol. Cancer Ther. 5, 246–252 (2006).

  104. 104

    Dong, Y., Zhang, H., Gao, A. C., Marshall, J. R. & Ip, C. Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers. Mol. Cancer Ther. 4, 1047–1055 (2005).

  105. 105

    Chan, J. M. et al. Plasma selenium, manganese superoxide dismutase, and intermediate- or high-risk prostate cancer. J. Clin. Oncol. 27, 3577–3583 (2009).

  106. 106

    Zhong, W. et al. Alteration of cellular phenotype and responses to oxidative stress by manganese superoxide dismutase and a superoxide dismutase mimic in RWPE-2 human prostate adenocarcinoma cells. Antioxid. Redox Signal. 6, 513–522 (2004).

  107. 107

    Shimoda-Matsubayashi, S. et al. Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene: A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson's disease. Biochem. Biophys. Res. Commun. 226, 561–565 (1996).

  108. 108

    Ellinger, S., Ellinger, J. & Stehle, P. Tomatoes, tomato products and lycopene in the prevention and treatment of prostate cancer: do we have the evidence from intervention studies? Curr. Opin. Clin. Nutr. Metab. Care 9, 722–727 (2006).

  109. 109

    Giovannucci, E. Tomato products, lycopene, and prostate cancer: a review of the epidemiological literature. J. Nutr. 135, 2030S–2031S (2005).

  110. 110

    Giovannucci, E., Rimm, E. B., Liu, Y., Stampfer, M. J. & Willett, W. C. A prospective study of tomato products, lycopene, and prostate cancer risk. J. Natl Cancer Inst. 94, 391–398 (2002).

  111. 111

    van Breemen, R. B. & Pajkovic, N. Multitargeted therapy of cancer by lycopene. Cancer Lett. 269, 339–351 (2008).

  112. 112

    Guns, E. S. & Cowell, S. P. Drug Insight: lycopene in the prevention and treatment of prostate cancer. Nat. Clin. Pract. Urol. 2, 38–43 (2005).

  113. 113

    Muzandu, K. et al. Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage. Jpn J. Vet. Res. 52, 173–184 (2005).

  114. 114

    Muzandu, K. et al. Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications. Toxicol. Appl. Pharmacol. 215, 330–340 (2006).

  115. 115

    Park, Y. O., Hwang, E. S. & Moon, T. W. The effect of lycopene on cell growth and oxidative DNA damage of Hep3B human hepatoma cells. Biofactors 23, 129–139 (2005).

  116. 116

    Erdman, J. W. Jr, Ford, N. A. & Lindshield, B. L. Are the health attributes of lycopene related to its antioxidant function? Arch. Biochem. Biophys. 483, 229–235 (2009).

  117. 117

    Ivanov, N. I. et al. Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines. Clin. Nutr. 26, 252–263 (2007).

  118. 118

    Hantz, H. L., Young, L. F. & Martin, K. R. Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells. Exp. Biol. Med. (Maywood) 230, 171–179 (2005).

  119. 119

    Liu, X., Allen, J. D., Arnold, J. T. & Blackman, M. R. Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells. Carcinogenesis 29, 816–823 (2008).

  120. 120

    Kanagaraj, P. et al. Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells. J. Cancer Res. Clin. Oncol. 133, 351–359 (2007).

  121. 121

    Siler, U. et al. Lycopene effects on rat normal prostate and prostate tumor tissue. J. Nutr. 135, 2050S–2052S (2005).

  122. 122

    Wertz, K., Siler, U. & Goralczyk, R. Lycopene: modes of action to promote prostate health. Arch. Biochem. Biophys. 430, 127–134 (2004).

  123. 123

    Edinger, M. S. & Koff, W. J. Effect of the consumption of tomato paste on plasma prostate-specific antigen levels in patients with benign prostate hyperplasia. Braz. J. Med. Biol. Res. 39, 1115–1119 (2006).

  124. 124

    Schwenke, C., Ubrig, B., Thurmann, P., Eggersmann, C. & Roth, S. Lycopene for advanced hormone refractory prostate cancer: a prospective, open phase II pilot study. J. Urol. 181, 1098–1103 (2009).

  125. 125

    Kirsh, V. A. et al. A prospective study of lycopene and tomato product intake and risk of prostate cancer. Cancer Epidemiol. Biomarkers Prev. 15, 92–98 (2006).

  126. 126

    Peters, U. et al. Serum lycopene, other carotenoids, and prostate cancer risk: a nested case–control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol. Biomarkers Prev. 16, 962–968 (2007).

  127. 127

    Kavanaugh, C. J., Trumbo, P. R. & Ellwood, K. C. The U. S. Food and Drug Administration's evidence-based review for qualified health claims: tomatoes, lycopene, and cancer. J. Natl Cancer Inst. 99, 1074–1085 (2007).

  128. 128

    Ambrosone, C. B. et al. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J. Nutr. 134, 1134–1138 (2004).

  129. 129

    Lin, H. J. et al. Glutathione transferase (GSTM1) null genotype, smoking, and prevalence of colorectal adenomas. Cancer Res. 55, 1224–1226 (1995).

  130. 130

    Spitz, M. R. et al. Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk. Cancer Epidemiol. Biomarkers Prev. 9, 1017–1020 (2000).

  131. 131

    Wang, L. I. et al. Dietary intake of cruciferous vegetables, glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population. Cancer Causes Control 15, 977–985 (2004).

  132. 132

    Joseph, M. A. et al. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr. Cancer 50, 206–213 (2004).

  133. 133

    Kristal, A. R. & Lampe, J. W. Brassica vegetables and prostate cancer risk: a review of the epidemiological evidence. Nutr. Cancer 42, 1–9 (2002).

  134. 134

    Kirsh, V. A. et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J. Natl Cancer Inst. 99, 1200–1209 (2007).

  135. 135

    Giovannucci, E., Rimm, E. B., Liu, Y., Stampfer, M. J. & Willett, W. C. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol. Biomarkers Prev. 12, 1403–1409 (2003).

  136. 136

    Hsing, A. W., Comstock, G. W., Abbey, H. & Polk, B. F. Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer. J. Natl Cancer Inst. 82, 941–946 (1990).

  137. 137

    Key, T. J. et al. Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int. J. Cancer 109, 119–124 (2004).

  138. 138

    Stram, D. O. et al. Prostate cancer incidence and intake of fruits, vegetables and related micronutrients: the multiethnic cohort study* (United States). Cancer Causes Control 17, 1193–1207 (2006).

  139. 139

    Singh, S. V. et al. Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J. Biol. Chem. 280, 19911–19924 (2005).

  140. 140

    Zhang, Y. Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action. Mutat. Res. 555, 173–190 (2004).

  141. 141

    Zhang, Y., Talalay, P., Cho, C. G. & Posner, G. H. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl Acad. Sci. USA 89, 2399–2403 (1992).

  142. 142

    Jones, S. B. & Brooks, J. D. Modest induction of phase 2 enzyme activity in the F-344 rat prostate. BMC Cancer 6, 62 (2006).

  143. 143

    Singh, A. V., Xiao, D., Lew, K. L., Dhir, R. & Singh, S. V. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis 25, 83–90 (2004).

  144. 144

    Juge, N., Mithen, R. F. & Traka, M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell. Mol. Life Sci. 64, 1105–1127 (2007).

  145. 145

    Jakubikova, J., Sedlak, J., Bod'o, J. & Bao, Y. Effect of isothiocyanates on nuclear accumulation of NF-κB, Nrf2, and thioredoxin in caco-2 cells. J. Agric. Food Chem. 54, 1656–1662 (2006).

  146. 146

    Xu, C. et al. ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells. Carcinogenesis 27, 437–445 (2006).

  147. 147

    Keum, Y. S. et al. Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent kinase pathway. Pharm. Res. 26, 2324–2331 (2009).

  148. 148

    Myzak, M. C., Hardin, K., Wang, R., Dashwood, R. H. & Ho, E. Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis 27, 811–819 (2006).

  149. 149

    Gibbs, A., Schwartzman, J., Deng, V. & Alumkal, J. Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc. Natl Acad. Sci. USA 106, 16663–16668 (2009).

  150. 150

    Mukhtar, H. & Ahmad, N. Tea polyphenols: prevention of cancer and optimizing health. Am. J. Clin. Nutr. 71 (6 Suppl.), 1698S–1702S (2000).

  151. 151

    Erba, D. et al. Effectiveness of moderate green tea consumption on antioxidative status and plasma lipid profile in humans. J. Nutr. Biochem. 16, 144–149 (2005).

  152. 152

    Khan, N. & Mukhtar, H. Tea polyphenols for health promotion. Life Sci. 81, 519–533 (2007).

  153. 153

    Khan, N. & Mukhtar, H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 269, 269–280 (2008).

  154. 154

    Bettuzzi, S. et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 66, 1234–1240 (2006).

  155. 155

    Brausi, M., Rizzi, F. & Bettuzzi, S. Chemoprevention of human prostate cancer by green tea catechins: two years later: a follow-up update. Eur. Urol. 54, 472–473 (2008).

  156. 156

    Choan, E. et al. A prospective clinical trial of green tea for hormone refractory prostate cancer: an evaluation of the complementary/alternative therapy approach. Urol. Oncol. 23, 108–113 (2005).

  157. 157

    Adhami, V. M. et al. Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo. Clin. Cancer Res. 13, 1611–1619 (2007).

  158. 158

    Siddiqui, I. A. et al. Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene 27, 2055–2063 (2008).

  159. 159

    Gupta, S., Ahmad, N., Nieminen, A. L. & Mukhtar, H. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol. Appl. Pharmacol. 164, 82–90 (2000).

  160. 160

    Gupta, S., Hastak, K., Afaq, F., Ahmad, N. & Mukhtar, H. Essential role of caspases in epigallocatechin-3-gallate-mediated inhibition of nuclear factor kappa B and induction of apoptosis. Oncogene 23, 2507–2522 (2004).

  161. 161

    Adhami, V. M., Siddiqui, I. A., Ahmad, N., Gupta, S. & Mukhtar, H. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer. Cancer Res. 64, 8715–8722 (2004).

  162. 162

    Hastak, K. et al. Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene 22, 4851–4859 (2003).

  163. 163

    Hastak, K., Agarwal, M. K., Mukhtar, H. & Agarwal, M. L. Ablation of either p21 or Bax prevents p53-dependent apoptosis induced by green tea polyphenol epigallocatechin-3-gallate. FASEB J. 19, 789–791 (2005).

  164. 164

    Sartor, L. et al. Prostate carcinoma and green tea: (-)epigallocatechin-3-gallate inhibits inflammation-triggered MMP-2 activation and invasion in murine TRAMP model. Int. J. Cancer 112, 823–829 (2004).

  165. 165

    Patel, S. P., Hotston, M., Kommu, S. & Persad, R. A. The protective effects of green tea in prostate cancer. BJU Int. 96, 1212–1214 (2005).

  166. 166

    Gupta, S., Hastak, K., Ahmad, N., Lewin, J. S. & Mukhtar, H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc. Natl Acad. Sci. USA 98, 10350–10355 (2001).

  167. 167

    Adhami, V. M. et al. Effective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on the stage of the disease. Clin. Cancer Res. 15, 1947–1953 (2009).

  168. 168

    Lawson, K. A. et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J. Natl Cancer Inst. 99, 754–764 (2007).

  169. 169

    Kumi-Diaka, J., Merchant, K., Haces, A., Hormann, V. & Johnson, M. Genistein–selenium combination induces growth arrest in prostate cancer cells. J. Med. Food 13, 1–9 (2010).

  170. 170

    Hasler, C. M. & Blumberg, J. B. Phytochemicals: biochemistry and physiology: introduction. J. Nutr. 129, 756S–757S (1999).

  171. 171

    Agarwal, R. Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention. Biochem. Pharmacol. 60, 1051–1059 (2000).

  172. 172

    Pezzato, E. et al. Prostate carcinoma and green tea: PSA-triggered basement membrane degradation and MMP-2 activation are inhibited by (-)epigallocatechin-3-gallate. Int. J. Cancer 112, 787–792 (2004).

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Venkateswaran, V., Klotz, L. Diet and prostate cancer: mechanisms of action and implications for chemoprevention. Nat Rev Urol 7, 442–453 (2010). https://doi.org/10.1038/nrurol.2010.102

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