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Vol. 74, No. 4, 2005
Issue release date: May 2005

Can We Prevent Prostate Cancer? Rationale and Current Status of Prostate Cancer Chemoprevention

Fujimoto N. · Chang C. · Nomura M. · Matsumoto T.
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Abstract

Prostate cancer has been one of the most frequent cancers among men in Western countries for the past decade. Investigation of prostate cancer prevention is very attractive, because prostate cancer has a high incidence, long-term natural history, regional difference in incidence, and is effected by sex steroids. Chemoprevention is defined as the use of specific agents to suppress or reverse carcinogenesis and to prevent the development of cancer. The development of chemoprevention strategies against prostate cancer would be of medical and economic importance. Basic and clinical research of chemoprevention of prostate cancer are under active investigation. This article aims to summarize and review the basic evidence and clinical trials on prostate cancer chemoprevention. Recent research has demonstrated that many agents, such as agents altering sex steroid signaling, drugs inducing antiproliferation/differentiation, retinoids, anti-inflammatory drugs, and antioxidants, could be potential preventatives for prostate cancer. Large-scale clinical trials have suggested that 5α-reductase inhibitor finasteride, selenium, and vitamin E can function as a chemopreventive agent. Although no definitely effective strategies of prostate cancer prevention have been identified yet, increasing evidence will provide effective and safe strategies that bring clinical benefits.



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References

  1. American Cancer Society: Cancer Facts and Figures 2004. Atlanta, American Cancer Society, 2004.
  2. Greenwald P, Kelloff GJ: The role of chemoprevention in cancer control; in Stewart BW, McGregor D, Kleihues P (eds): Principles of Chemoprevention. IARC Sci Publ No 139. Lyon, IARC, 1996, pp 13–22.
  3. Lieberman R: Androgen deprivation therapy for prostate cancer chemoprevention: Current status and future directions for agent development. Urology 2001;58(suppl 2A):83–90.
  4. Lieberman R: Evolving strategies for prostate cancer chemoprevention trials. World J Urol 2003;21:3–8.
  5. http://www.nci.nih.gov/search/ResultsClinicalTrials.aspx?protocolsearchid
  6. Thompson IM, Goodman PJ: The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349:215–224.
  7. Civantos F, Soloway MS, Pinto J: Histopathological effects of androgen deprivation in prostatic cancer. Semin Urol Oncol 1996;14(suppl 2):22–31.

    External Resources

  8. Bostwick DG: Prostatic adenocarcinoma following androgen deprivation therapy: The new difficulty in histologic interpretation. Anat Pathol 1998;3:1–16.
  9. Ishikawa S, Soloway M S, Van der Zwaag R, Todd B: Prognostic factors in survival free of progression after androgen deprivation therapy for treatment of prostate cancer. J Urol 1989;141:1139–1142.
  10. Hoffman MA, DeWolf WC Morgentaler A: Is low serum free testosterone a marker for high grade prostate cancer? J Urol 2000;163:824–827.
  11. Schatzl G, Madersbacher S, Haitel A, Gsur A, Preyer M, Haidinger G, Gassner C, Ochsner M, Marberger M: Association of serum testosterone with microvessel density, androgen receptor gene polymorphism in prostate cancer. J Urol 2003;169:1312–1315.
  12. Shibata Y, Ito K, Suzuki K, Nakano K, Fukabori Y, Suzuki, R, Kawabe Y, Honma S, Yamanaka H: Changes in the endocrine environment of the human prostate transition zone with aging: Simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition. Prostate 2000;42:25–55.

    External Resources

  13. Ross R, Bernstein L, Judd H, Hanisch R, Pike M, Henderson B: Serum testosterone levels in healthy young black and white men. J Natl Cancer Inst 1986;76:45–48.
  14. Moore RJ, Gazac JM, Wilson JD: Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17β-estradiol. J Clin Invest 1979;63:351–357.
  15. Mobbs BG, Johnson IE, Connolly JG, Thompson J: Concentration and cellular distribution of androgen receptor in human prostatic neoplasia: Can estrogen treatment increase androgen receptor content? J Steroid Biochem 1983;19:1279–1290.
  16. Blanchere M, Berthaut I, Portois MC, Mestayer C, Mowszowicz I: Hormonal regulation of the androgen receptor expression in human prostatic cells in culture. J Steroid Biochem Mol Biol 1998;66:319–326.
  17. Leav I, Ho SM, Ofner P, Merk FB, Kwan PW, Damassa D: Biochemical alterations in sex hormone-induced hyperplasia and dysplasia of the dorsolateral prostates of Noble rats. J Natl Cancer Inst 1988;80:1045–1053.
  18. Leave I, Merk FB, Kwan PW, Ho SM: Androgen-supported estrogen-enhanced epithelial proliferation in the prostates of intact Noble rats. Prostate 1989;15:23–40.
  19. Ofner P, Bosland MC, Vena RL: Differential effects of diethylstilbesterol and estradiol-17β in combination with testosterone on rat prostate lobes. Toxicol Appl Pharmacol 1992;112:300–309.
  20. Lau K, Leav I, Ho SM: Rat estrogen receptor-α and -β and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the Noble rats. Endocrinology 1998;139:424–427.
  21. Ho SM, Lee KF, Lane K: Neoplastic transformation of the prostate; in Naz RK (ed): Prostate: Basic and Clinical Aspects. New York, CRC Press, 1997, pp 74–114.
  22. Waters DJ, Bostwick DG: The canine prostate is a spontaneous model of intraepithelial neoplasia and prostate cancer progression. Anticancer Res 1997;17:1467–1470.
  23. Price KR, Fenwick GR: Naturally occurring oestrogens in foods – A review. Food Addit Contam 1985;2:73–106.
  24. Denis L, Morton MS, Griffiths K: Diet and its preventive role in prostatic disease. Eur Urol 1999;35:377–387.
  25. Raghow S, Hooshdaran MZ, Katiyar S, Steiner MS: Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse model. Cancer Res 2002;62:1370–1376.
  26. Steiner MS: The role of peptide growth factors in the prostate: A review. Urology 1993;42:99–110.
  27. Steiner MS: Review of peptide growth factors in benign prostatic hyperplasia and urologic malignancy. J Urol 1995;153:1085–1096.
  28. Lam HY: Tamoxifen is a calmodulin antagonist in the activation of cAMP phosphodiesterase. Biochem Biophys Res Commun 1984;118:27–32.
  29. Rohlff C, Blagosklonny M V, Kyle E, Kesari A, Kim I Y, Zelner D J, Hakim F, Trepel J, Bergan RC: Prostate cancer cell growth inhibition of protein kinase C and induction of p21(waf1/cip1). Prostate 1998;37:51–59.
  30. Steiner MS, Pound CR, Gingrich JR, Patterson Al, Wake RW, Conrad LW, Kisber RH, McSwain M, Shelton T: Acapodene (GTx-006) reduces high grade prostate intraepithelial neoplasia (HGPIN) in phase II clinical trial. Abstr 38th Annual Meeting American Society of Clinical Oncology, Orlando 2002, pp 18–21, abstr 719.
  31. Kim IY, Kim BC, Seong DH, Lee DK, Seo JM, Hong YJ, Kim HT, Morton RA, Kim SJ: Raloxifen, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines. Cancer Res 2002;62:5365–5369.
  32. Rao CV, Tokumo K, Rigotty J, Zang E, Kelloff G, Reddy BS: Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, α-difluoromethylornithine, 16α-fluoro-5-androsten-17-one, and ellagic acid individually and in combination. Cancer Res 1991;51:4528–4534.
  33. Ratko TA, Detrisac CJ, Rao KV, Thomas CF, Kelloff GJ, Moon RC: Interspecies analysis of the chemopreventive efficacy of dietary α-difluoromethylornithine. Anticancer Res 1990;10:67–72.
  34. Heston WD, Kadmon D, Lazan DW, Fair WR: Copenhagen rat prostatic tumor ornithine decarboxylase activity (ODC) and the effect of the ODC inhibitor α-difluoromethylornithine. Prostate 1982;3:383–389.
  35. Rao KV, Johnson WD, Bosland MC, Lubet RA, Steele VE, Kelloff GJ, McCormick DL: Chemoprevention of rat prostate carcinogenesis by early and delayed administration of dehydroepiandrosterone. Cancer Res 1999;59:3084–3089.
  36. Ciolino HP, Yeh GC: The steroid hormone dehydroepiandrosterone inhibits CYP1A1 expression in vitro by a post-transcriptional mechanism. J Biol Chem 1999;274:35186–35190.
  37. Trump DL: Retinoids in bladder, testis and prostate cancer: Epidemiologic, pre-clinical and clinical observations. Leukemia 1994;8(suppl 3):50–54.
  38. Peehl DM, Wong ST, Stamey TA: Vitamin A regulates proliferation and differentiation of human prostatic epithelial cells. Prostate 1993;23:69–78.
  39. Samid D, Shack S, Myers CE: Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J Clin Invest 1993;91:2288–2295.
  40. Carducci MA, Nelson JB, Chan-Tack KM, Ayyagari SR, Sweatt WH, Campbell PA, Nelson WG, Simons JW: Phenylbutyrate induces apoptosis in human prostate cancer and is more potent than phenylacetate. Clin Cancer Res 1996;2:379–387.
  41. Pineau T, Hudgins WR, Liu L, Chen LC, Sher T, Gonzalez FJ, Samid D: Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs. Biochem Pharmacol 1996;52:659–667.
  42. Franco OE, Onishi T, Umeda Y, Soga N, Wakita T, Arima K, Yanagawa M, Sugimura Y: Phenylacetate inhibits growth and modulates cell cycle gene expression in renal cancer cell lines. Anticancer Res 2003;23:1637–1642.
  43. Carducci MA, Gilbert J, Bowling MK, Noe D, Eisenberger MA, Sinibaldi V, Zabelina Y, Chen TL, Grochow LB, Donehower RC: A phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-hour infusion schedule. Clin Cancer Res 2001;7:3047–3055.
  44. Kirschenbaum A, Liu X, Yao S, Levine AC: The role of cyclooxygenase-2 in prostate cancer. Urology 2001;58(suppl 1):127–131.
  45. Kamijo T, Sato T, Nagatomi Y, Kitamura T: Induction of apoptosis by cyclooxygenase-2 inhibitors in prostate cancer cell lines. Int J Urol 2001;8:S35–S39.

    External Resources

  46. Johnson AJ, Song X, Hsu A, Chen C: Apoptosis signaling pathways mediated by cyclooxygenase-2 inhibitors in prostate cancer cells. Adv Enzyme Regul 2001;41:221–235.
  47. Liu XH, Kirschenbaum A, Yao S, Lee R, Holland JF, Levine AC: Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 2000;164:820–825.
  48. Pan Y, Zhang JS, Gazi MH, Young CY: The cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs celecoxib and nimesulide inhibit androgen receptor activity via induction of c-Jun in prostate cancer cells. Cancer Epidemiol Biomarkers Prev 2003;12:769–774.
  49. Gupta S, Adhami VM, Subbarayan M, MacLennan GT, Lewin JS, Hafeli UO, Fu P, Mukhtar H: Suppression of prostate carcinogenesis by dietary supplementation of celecoxib in transgenic adenocarcinoma of the mouse prostate model. Cancer Res 2004;64:3334–3343.
  50. Reddy BS, Hirose Y, Lubet R, Steele V, Kelloff G, Paulson S, Seibert K, Rao CV: Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administrated during different stages of carcinogenesis. Cancer Res 2000;60:293–297.
  51. Kawamori T, Rao CV, Seibert K, Reddy BS: Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998;58:409–412.
  52. Burke CA, Bauer WM, Lashner B: Chemoprevention of colorectal cancer: Slow, steady progress. Cleve Clin J Med 2003;70:346–350.
  53. Stoner GD, Budd GT, Ganapathi R, DeYoung B, Kresty LA, Nitert M, Fryer B, Church JM, Provencher K, Pamukcu R, Piazza G, Hawk E, Kelloff G, Elson P, van Stolk RU: Sulindac sulfone induced regression of rectal polyps in patients with familial adenomatous polyposis. Adv Exp Med Biol 1999;470:45–53.
  54. Thompson HJ, Briggs S, Paranka NS: Sulfone metabolite of sulindac inhibits mammary carcinogenesis. J Natl Cancer Inst 1995;85:1259–1261.

    External Resources

  55. Thompson HJ, Jiang C, Lu J, Mehta RG, Piazza GA, Paranka NS, Pamukcu R: Sulfone metabolite of sulindac inhibits mammary carcinogenesis. Cancer Res 1997;57:267–271.
  56. Piazza GA, Alberts DS, Hixson LJ, Paranka NS, Li H, Finn T, Bogert C, Guillen JM, Brendel K, Gross PH, Sperl G, Ritchie J, Burt RW, Ellsworth L, Ahnen DJ, Pamukcu R: Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels. Cancer Res 1997;57:2909–2915.
  57. Malkinson AM, Koski KM, Dwyer-Nield LD, Rice PL, Rioux N, Castonguay A, Ahnen DJ, Thompson H, Pamukcu R, Piazza GA: Inhibition of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone-induced mouse lung tumor formation by FGN-1 (sulindac sulfone). Carcino genesis 1998;8:1353–1356.
  58. Piazza GA, Thompson WJ, Pamukcu R, Alila HW, Whitehead CM, Liu L, Fetter JR, Gresh WE Jr, Klein-Szanto AJ, Farnell DR, Eto I, Grubbs CJ: Exisulind, a novel proapoptotic drug, inhibits rat urinary bladder tumorigenesis. Cancer Res 2001;61:3961–3968.
  59. Lim JT, Piazza GA, Han EK, Delohery TM, Li H, Finn TS, Buttyan R, Yamamoto H, Sperl GJ, Brendel K, Gross PH, Pamukcu R, Weinstein IB: Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines. Biochem Pharmacol 1999;58:1097–1107.
  60. Goluboff ET, Shabsigh A, Saidi JA, Weinstein IB, Mitra N, Heitjan D, Piazza GA, Pamukcu R, Buttyan R, Olsson CA: Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis. Urology 1999;53:440–445.
  61. Halliwell B: Free radicals and antioxidants: A personal view. Nutr Rev 1994;52:253–265.
  62. Ripple MO, Henry WF, Rago RP, Wilding G: Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells. J Natl Cancer Inst 1997;89:40–48.
  63. Halliwell B: Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence? Lancet 1994;344:721–724.
  64. Toledano MB, Leonald WJ: Modulation of transcription factor NFkB binding activity by oxidation-reduction in vitro. Proc Natl Acad Sci USA 1991;88:4328–4332.
  65. Wei H: Activation of oncogenes and or inactivation of anti-oncogenes by reactive oxygen species. Med Hypotheses 1992;39:267–270.
  66. Hainaut P, Milner J: Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res 1993;53:4469–4473.
  67. Nakamura A, Shirai T, Takahashi S, Ogawa K, Hirose M, Ito N: Lack of modification by naturally occurring antioxidants of 3,2′-dimethyl-4-aminobiphenyl initiated rate prostate carcinogenesis. Cancer Lett 1991;58:241–246.
  68. Webber MM, Perez-Ripoli EA, James GT: Inhibitory effects of selenium on the growth of DU145 human prostate carcinoma cells in vitro. Biochem Biophys Res Commun 1985;130:603–609.
  69. Ip C, Medina D: Current concept of selenium and mammary tumorigenesis; in Medina D, Kidwell W, Heppner G, Anderson EP (eds): Cellular and Molecular Biology of Breast Cancer. New York, Plenum Press, 1987, p 479.
  70. Kiremindjian-Scheumacher L, Stotzky G: Review: Selenium and immune response. Environ Res 1987;42:277–303.
  71. Thompson HJ, Wilson A, Lu J, Singh M, Jiang C, Upadhyaya P, el-Bayoumy K, Ip C: Comparison of the effects of an organic and an inorganic form of selenium on a mammary carcinoma cell line. Carcinogenesis 1994;15:183–186.
  72. Redman C, Scott JA, Baines AT, Basye JL, Clark LC, Calley C, Roe D, Payne CM, Nelson MA: Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines. Cancer Lett 1998;125:103–110.
  73. Shimada T, El-Bayoumy K, Upadhyaya P, Sutter TR, Guengerich FP, Yamazaki H: Inhibition of human cytochrome P450-catalyzed oxidations of xenobiotics and procarcinogens by synthetic organoselenium compounds. Cancer Res 1997;57:4757–4764.
  74. El-Bayoumy K: The role of selenium in cancer prevention; in DeVita VT, Hellman S, Rosenberg SS (eds): Practice of Oncology. Philadelphia,Lippincott, 1991, pp 1–15.
  75. Bedwal RS, Nair N, Sharma MP, Mathurk RS: Selenium – Its biological perspectives. Med Hypotheses 1993;41:150–159.
  76. Day NE, Bingham SA: Re: Nutrition intervention trials in Linxian, China: Supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1994;86:1645–1638.
  77. Li JY, Taylor PR, Li B, Dawsey S, Wang GQ, Ershow AG, Guo W, Liu SF, Yang CS, Shen Q: Nutrition intervention trials in Linxian, China: Multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J Natl Cancer Inst 1993;85:1492–1498.
  78. 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 1998;90:1219–1224.
  79. 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. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 1996;276:1957–1963.
  80. Burton GW, Foster DO, Perly B, Slater TF, Smith IC, Ingold KU: Biological antioxidants. Philos Trans R Soc Lond B Biol Sci 1985;311:565–578.
  81. Fleshner NE, Kucuk O: Antioxidant dietary supplements: Rationale and current status as chemopreventive agents for prostate cancer. Urology 2001;57(suppl 4A):90–94.
  82. Mahoney CW, Azzi A: Vitamin E inhibits protein kinase C activity. Biochem Biophys Res Commun 1998;154:694–697.
  83. Chatelain E, Boscoboinik DO, Bartoli GM, Kagan VE, Gey FK, Packer L, Azzi A: Inhibition of smooth muscle cell proliferation and protein kinase C activity by tocopherols and tocotrienols. Biochim Biophys Acta 1993;1176:83–89.
  84. Wang W, Higuchi CM: Induction of NAD(P)H: Quinone reductase by vitamins A, E and C in Colo205 colon cancer cells. Cancer Lett 1995;98:63–69.
  85. Traber MG, Packer L: Vitamin E: Beyond antioxidant function. Am J Clin Nutr 1995;62:1501–1509.
  86. Hsing A W, Comstock GW, Abbey H, Polk BF: Serologic precursors of cancer retinol, carotenoids, and tocopherol and risk of prostate cancer. J Natl Cancer Inst 1990;82:941–946.
  87. 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 α-tocopherol and b-carotene: Incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440–446.
  88. Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR, Coltman C: SELECT: The next prostate cancer prevention trial. J Urol 2001;166:1311–1315.
  89. Stahl W, Nicolai S, Briviba K, Hanusch M, Broszeit G, Peters M, Martin HD, Sies H: Biological activities of natural and synthetic carotenoids: Induction of gap junctional communication and singlet oxygen quenching. Carci nogenesis 1997;18:89–92.
  90. Heber D, Lu QY: Overview of mechanisms of action of lycopene. Exp Biol Med 2002;227:920–923.
  91. Aust O, Ale-Agha N, Zhang L, Wollersen H, Sies H, Stahl W: Lycopene oxidation product enhances gap junctional communication. Food Chem Toxicol 2003;41:1399–407.
  92. Mills PK, Beeson WL, Phillips RL, Fraser GE: Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 1989;64:598–604.
  93. Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Giovannucci E, Ascherio A, Rimm E: Intake of carotenoids and retinol in relationship to risk of prostate cancer. J Natl Cancer Inst 1995;87:1767–1776.
  94. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N: Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:1371–1388.


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