Selenium and Androgen Receptor in Prostate Cancer



Prostate cancer chemoprevention has generated considerable interest in the last decade and selenium and combinations of selenium have been recognized as one of the most efficacious chemopreventive agents against prostate cancer. This chapter focuses on a discussion of the findings regarding the mechanisms of action of various selenium compounds and their effects on cellular processes and signaling pathways, particularly on androgen signaling. We also describe the clinical and preclinical studies that have contributed enormously to the knowledge about dose, duration of exposure, and the chemical form of selenium effective in different scenarios. The initial analysis of the SELECT study found that 200 μg of selenium and 400 IUs daily of vitamin E do not prevent prostate cancer even though a 2002 follow-up report showed that men who took selenium for more than 7§ years had about 52 percent fewer new cases of prostate cancer than men who took placebo. This raises concerns about the efficacy of the use of selenomethionine in the trial as the source of selenium and underscores the importance of choosing the chemical form and dosage of selenium supplementation with care. Even though popular opinion is still undecided about whether selenium can be used as a chemopreventive agent in the clinic and whether studies with cell lines and populations at low, medium, or high risk can adequately represent the physiological behavior of this micronutrient, it can safely be said to offer the most diverse spectrum of protective effects against prostate cancer which warrants for its future as a chemopreventive agent. A more diverse analysis of the effects of selenium on androgen receptor signaling and related pathways would shed more light on its role in prevention of prostate cancer progression rather than initiation.


Prostate Cancer Androgen Receptor Prostate Cancer Cell LNCaP Cell Prostate Cancer Risk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by NIH grants CA118887 and CA109441 (Gao AC).


  1. Aarnisalo P, Palvimo JJ, Janne OA (1998) CREB-binding protein in androgen receptor-mediated signaling. Proc Natl Acad Sci USA. 95: 2122–2127.PubMedGoogle Scholar
  2. Abreu-Martin MT, Chari A, Palladino AA, et al. (1999) Mitogen activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer. Mol Cell Biol 19: 5143–5144.PubMedGoogle Scholar
  3. Alexander J (2007) Selenium. Novartis Found Symp 282: 143–149.PubMedGoogle Scholar
  4. Allen NE, Morris JS, Ngwenyama RA, et al. (2004) A case-control study of selenium in nails and prostate cancer risk in British men. J Cancer 90(7): 1392–1396.Google Scholar
  5. Al-Taie OH, Suefert J, Mork H, et al. (2002) A complex DNA-repeat structure within the selenoprotein P promoter contains a functionally relevant polymorphism and is genetically unstable under conditions of mismatch repair deficiency. Eur J Hum Genet 10(9): 499–504.PubMedGoogle Scholar
  6. Asim M, Siddiqui IA, Hafeez BB, et al. (2008) Src kinase potentiates androgen receptor transactivation function and invasion of androgen-independent prostate cancer C4–2 cells. Oncogene (EPub) 1–9.Google Scholar
  7. Brooks JD, Metter EJ, Chan DW, et al. (2001) Plasma selenium level before diagnosis and the risk of prostate cancer development. J Urol 166: 2034–2038.PubMedGoogle Scholar
  8. Calvo A, Xiao N, Kang J, et al. (2002) Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors. Cancer Res 62(18): 5325–5335.PubMedGoogle Scholar
  9. Chan JM, Stampfer MJ, Giovanucci E, et al. (1998) Plasma insulin-like growth factor-1 and prostate cancer risk: a prospective study. Science 279: 563–566.PubMedGoogle Scholar
  10. Chatterjee B (2003) The role of the androgen receptor in the development of prostatic hyperplasia and prostate cancer. Mol Cell Biochem 253(1–2): 89–101.PubMedGoogle Scholar
  11. Chen SD, Welsbie DS, Tran C, et al. (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10: 33–39.PubMedGoogle Scholar
  12. Chmelar R, Buchanan G, Need EF, et al. (2006) Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer 120: 719–733.Google Scholar
  13. Cho SD, Jiang C, Malewicz B, et al. (2004) Methyl selenium metabolites decrease prostate specific antigen expression by inducing protein degradation and suppressing androgen-stimulated transcription. Mol Cancer Ther 3(5): 605–611.PubMedGoogle Scholar
  14. Christensen MJ, Nartey ET, Hada AL, et al. (2007) High selenium reduces NF-kappaB-regulated gene expression in uninduced human prostate cancer cells. Nutr Cancer 58(2): 197–204.PubMedGoogle Scholar
  15. Chun JY, Nadiminty N, Lee SO, et al. (2006) Mechanisms of selenium down-regulation of androgen receptor signaling in prostate cancer. Mol Cancer Ther 5(4): 913–918.PubMedGoogle Scholar
  16. Clark LC, Jacobs ET (1998) Environmental selenium and cancer: risk or protection? Cancer Epidemiol Biomarkers Prev 7(10): 847–848.PubMedGoogle Scholar
  17. Clark LC, Marshall JR (2001) Randomized, controlled chemoprevention trials in populations at very high risk for prostate cancer: elevated prostate specific antigen and high-grade prostatic intraepithelial neoplasia. Urology 57: 185–187.PubMedGoogle Scholar
  18. Clark LC, Combs GF Jr, Turnbull BW, et al. (1996) 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 276(24): 1957–1963.PubMedGoogle Scholar
  19. Clark LC, Dalkin B, Krongrad A, et al. (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 81(5): 730–734.PubMedGoogle Scholar
  20. Combs GF Jr (2001) Considering the mechanisms of cancer prevention by selenium. Adv Exp Med Biol 492: 107–117.PubMedGoogle Scholar
  21. Combs GF (2004) Status of selenium in prostate cancer prevention. Br J Cancer 91: 195–199.PubMedGoogle Scholar
  22. Combs GF Jr, Combs SB (1984) The nutritional biochemistry of selenium. Annu Rev Nutr 4: 257–280.PubMedGoogle Scholar
  23. Combs GF, Gray WP (1998) Chemopreventive agents:selenium. Pharmacol Ther 79: 179–192.PubMedGoogle Scholar
  24. Combs GF, Clark LC, Turnbull BW (1997) Reduction of cancer risk with an oral supplement of selenium. Biomed Environ Sci 10(2–3): 227–234.PubMedGoogle Scholar
  25. Corcoran NM, Najdovska M, Costello AJ (2004) Inorganic selenium retards progression of experimental hormone refractory prostate cancer. J Urol 171: 907–910.PubMedGoogle Scholar
  26. Costello AJ (2001) A randomized, controlled chemoprevention trial of selenium in familial prostate cancer: Rationale, recruitment and design issues. Urology 57(4A): 182–184.PubMedGoogle Scholar
  27. Craft N, Shostak K, Carey M, et al. (1999) A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med 5:280–285.PubMedGoogle Scholar
  28. Culig Z, Hobisch A, Cronauer MV, et al. (1994) Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor and epidermal growth factor. Cancer Res 54: 5474–5478.PubMedGoogle Scholar
  29. D'amico F, Biancolella M, Margiotti K, et al. (2007) Genomic biomarkers, androgen pathway and prostate cancer. Pharmacogenomics 8(6): 645–661.PubMedGoogle Scholar
  30. de Jong FH, Reuvers PJ, Bolt-de Vries J, et al. (1992) Androgens and androgen receptors in prostate tissue from patients with benign prostatic hyperplasia: effects of cyproterone acetate. J Steroid Biochem Mol Biol 52: 49–55.Google Scholar
  31. Dewaily E, Mulvad G, Sloth Pedersen H, et al. (2003) Inuit are protected against prostate cancer. Cancer Epidemiol Biomarkers Prev 12(9): 926–927.Google Scholar
  32. Diwadkar-Navsariwala V, Prins GS, Swanson SM, et al. (2006) Selenoprotein.deficiency accelerates prostate carcinogenesis in a transgenic model. Proc Natl Acad Sci USA 103: 8179–8184.PubMedGoogle Scholar
  33. Dong Y, Zhang H, Hawthorn L, et al. (2003) Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array. Cancer Res 63(1): 52–59.PubMedGoogle Scholar
  34. Dong Y, Lee SO, Zhang H, et al. (2004) Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling. Cancer Res 64(1): 19–22.PubMedGoogle Scholar
  35. Dong Y, Zhang H, Gao AC, et al. (2005) 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(7): 1047–1055.PubMedGoogle Scholar
  36. Drake EN (2006) Cancer chemoprevention: selenium as a prooxidant, not an antioxidant. Med Hypotheses 67(2): 318–322.PubMedGoogle Scholar
  37. Drasch G, Mail der S, Schlosser C, et al. (2000) Content of non-mercury associated selenium in human tissues. Biol Trace Elem Res 77: 219–230.PubMedGoogle Scholar
  38. Duffield AJ, Thomson CD, Hill KE, et al. (1999) An estimation of selenium requirements for New Zealanders. Am J Clin Nutr 70: 896–903.PubMedGoogle Scholar
  39. Duffield-Lillico AJ, Dalkin BL, Reid ME, et al. (2003) Nutritional Prevention of Cancer Study group, Selenium-supplementation, baseline plasma selenium levels and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int 91(7): 608–612.PubMedGoogle Scholar
  40. El-Bayoumy K, Sinha R (2005) Molecular chemoprevention by selenium: A genomic approach. Mutat Res 591: 224–236.PubMedGoogle Scholar
  41. Eng J, Ramsum D, Verhoef M, et al. (2003) A population-based survey of complementary and alternative medicine use in men recently diagnosed with prostate cancer. Integr Cancer Ther 2(3): 212–216.PubMedGoogle Scholar
  42. Fu M, Wang C, Wang J, et al. (2002) Androgen receptor acetylation governs transactivation and MEKK-1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol Cell Biol 22: 3373–3388.PubMedGoogle Scholar
  43. Fu M, Wang C, Li Z, et al. (2004) Minireview: Cyclin D1: Normal and abnormal functions. Endocrinology 145(12): 5439–5447.PubMedGoogle Scholar
  44. Gasparian AV, Yao YJ, Lu J, et al. (2002) Selenium compounds inhibit IkappaB kinase (IKK) and nuclear factor-kappa B (NF-kappa B) in prostate cancer cells. Mol Cancer Ther 1(12): 1079–1087.PubMedGoogle Scholar
  45. Ghosh J (2004) Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase. Biochem Biophy Res Commun 315: 624–635.Google Scholar
  46. Gianduzzo TR, Holmes EG, Tinggi U, et al. (2003) Prostatic and peripheral blood selenium levels after oral supplementation. J Urol 170(3): 870–873.PubMedGoogle Scholar
  47. Goodman GE, Schaffer S, Bankson DD, et al. & the Carotene and Retinol Efficacy Trial (CARET) Co-investigators (2001) Predictors of serum in cigarette smokers and the lack of association with lung and prostate cancer risk. Cancer Epidemiol Biomarkers Prev 10: 1069–1076.PubMedGoogle Scholar
  48. Grossmann ME, Huang H, Tindall TJ (2001) Androgen receptor signaling in androgen refractory prostate cancer. J Natl Cancer Inst 22: 1687–1697.Google Scholar
  49. Haapala K, Kuukasjarvi T, Hyytinen E, et al. (2007) Androgen receptor amplification is associated with increased cell proliferation in prostate cancer. Hum Pathol 38: 474–478.PubMedGoogle Scholar
  50. Harada S, Keller ET, Fujimoto N, et al. (2001) Long-term exposure of tumor necrosis factor alpha causes hypersensitivity to androgen and anti-androgen withdrawal phenomenon in LNCaP prostate cancer cells. Prostate 46: 319–326.PubMedGoogle Scholar
  51. Helzslouer KJ, Huang H-Y, Alberg AJ, et al. (2000) Association between alpha-tocopherol, gamma-tocopherol, selenium and subsequent prostate cancer. J Natl Cancer Inst 92: 2018–2023.Google Scholar
  52. Hobisch A, Eder IE, Putz T, et al. (1998) Interleukin-6 regulates prostate specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res 58: 4640–4645.PubMedGoogle Scholar
  53. Hu YJ, Korotkov KV, Mehta R, et al. (2001) Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene. Cancer Res 61(5): 2307–2310.PubMedGoogle Scholar
  54. Hu H, Jiang C, Li G, et al. (2005) PKB/Akt and Erk regulation of caspase-mediated apoptosis by methylseleninic acid in LNCaP prostate cancer cells. Carcinogenesis 26(8): 1374–81.PubMedGoogle Scholar
  55. Hu H, Jiang C, Schuster T, et al. (2006) Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis through superoxide/p53/Bax-mediated activation of the mitochondrial pathway. Mol. Cancer Ther 5(7): 1873–1882.PubMedGoogle Scholar
  56. Husbeck B, Peehl DM, Knox SJ (2005) Redox modulation of human prostate carcinoma cells by selenite increases radiation-induced cell killing. Free Radic Biol Med 38(1): 50–57.PubMedGoogle Scholar
  57. Husbeck B, Bhattacharya RS, Feldman D, et al. (2006a) Inhibition of androgen receptor signaling by selenite and methylseleninic acid in prostate cancer cells: two distinct mechanisms of action. Mol Cancer Ther 5(8): 2078–2085.Google Scholar
  58. Husbeck B, Nonn L, Peehl DM, et al. (2006b) Tumor-selective killing by selenite in patient-matched pairs of normal and malignant prostate cells. Prostate 66(2): 218–225.Google Scholar
  59. Ip C (1998) Lessons from basic research in selenium and cancer prevention. J Nutr 128: 1845–1854.PubMedGoogle Scholar
  60. Ip C, Thompson HJ, Zhu Z, et al. (2000) In vitro and in vivo studies of methylseleninic acid: evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention. Cancer Res 60(11): 2882–2886.PubMedGoogle Scholar
  61. Javidan J, Deitch A, Shi XB, et al. (2005) The androgen receptor and mechanisms for androgen independence in prostate cancer. Cancer Invest 23(6): 520–528.PubMedGoogle Scholar
  62. Jiang C, Jiang W, Ip C, et al. (1999) Selenium-induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake. Mol Carcinog 26(4): 213–225.PubMedGoogle Scholar
  63. Jiang C, Ganther H, Lu J (2000a) Monomethylselenium – specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Mol Carcinog 29(4): 236–250.Google Scholar
  64. Jiang C, Wang Z, Ganther H, et al. (2000b) Caspases as key regulators of methyl selenium-induced apoptosis (anoikis) of DU 145 prostate cancer cells. Cancer Res 61(7): 3062–3070.Google Scholar
  65. Jin RJ, Wang Y, Masumori N, et al. (2004) NE-10 neuroendocrine cancer promotes the LNCaP xenografts growth in castrated mice. Cancer Res 64: 5489–5495.PubMedGoogle Scholar
  66. Kaarbo M, Klokk TI, Saatcioglu F (2007) Androgen signaling and its interactions with other signaling pathways in prostate cancer. BioEssays 29: 1227–1238.PubMedGoogle Scholar
  67. Karin M, Cao Y, Greten FR, et al. (2002) NF-kappaB in cancer: from innocent by-stander to major culprit. Nature Rev Cancer 2: 301–310.Google Scholar
  68. Karunasinghe N, Ryan J, Tuckey J, et al. (2004) DNA stability and serum selenium levels in a high risk group for prostate cancer. Cancer Epidemiol Biomarkers Prev 13(3): 391–397.PubMedGoogle Scholar
  69. Kawabe T (2004) G2 checkpoint abrogators as anticancer drugs. Mol Cancer Ther 3(4): 513–519.PubMedGoogle Scholar
  70. Klein EA (2004) Selenium and Vitamin E cancer prevention trial. Ann NY Acad Sci 1031: 234–41.PubMedGoogle Scholar
  71. Klein EA, Thompson IM (2004) Update on chemoprevention of prostate cancer. Curr Opin Urol 14: 143–149.PubMedGoogle Scholar
  72. Knekt P, Aromaa A, Maatela J, et al. (1990) Serum selenium and subsequent risk of cancer among Finnish men and women. J Natl Cancer Inst 82: 864–868.PubMedGoogle Scholar
  73. Konishi N, Shimada K, Ishida E, et al. (2005) Molecular pathology of cancer. Pathol Int 55: 531–539.PubMedGoogle Scholar
  74. Korotkov KV, Kumaraswamy E, Zhou Y, et al. (2001) Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells. J Biol Chem 276(18): 15330–15336.PubMedGoogle Scholar
  75. Kranse R, Dagnelie PC, van Kemenade M, et al. (2005) Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study. Int J Cancer 113(5): 835–840.PubMedGoogle Scholar
  76. Kryukov GV, Castellano S, Novoselov SV, et al. (2003) Characterization of mammalian selenoproteomes. Science 300: 1439–1443.PubMedGoogle Scholar
  77. Kumaraswamy E, Malykh A, Korotkov KV, et al. (2000) Structure-expression relationships of the 15 kDa selenoprotein gene. Possible role of the protein in cancer etiology. J Biol Chem 275(45): 35540–35547.PubMedGoogle Scholar
  78. Lee SO, Chun JY, Nadiminty N, et al. (2006) Monomethylated selenium inhibits growth of LNCaP human prostate cancer xenografts accompanied by a decrease in the expression of androgen receptor and prostate specific antigen (PSA). Prostate 66(10): 1070–1075.PubMedGoogle Scholar
  79. Li H, Stampfer MJ, Giovanucci EL, et al. (2004) A prospective study of plasma selenium levels and prostate cancer risk. J Natl Cancer Inst 96: 696–703.PubMedGoogle Scholar
  80. Li G-X, Hu H, Jiang C, et al. (2007) Differential involvement of reactive oxygen species in apoptosis induced by two classes of selenium compounds in human prostate cancer cells. Int J Cancer 120: 2034–2043.PubMedGoogle Scholar
  81. Liao Y, Abel U, Grobholz R, et al. (2005) Up-regulation of insulin-like growth factor axis components in human primary prostate cancer correlates with tumor grade. Human Pathology 36: 1186–1196.PubMedGoogle Scholar
  82. Lipsky K, Zigeuner R, Zischka M, et al. (2004) Selenium levels of patients with newly diagnosed prostate cancer compared with control group. Urology 63(5): 912–916.PubMedGoogle Scholar
  83. Lorenzo GD, Bianco R, Tortora G, et al. (2003) Involvement of growth factor receptors of the epidermal growth factor receptor family in prostate cancer development and progression to androgen independence. Clin Prostate Cancer 2: 50–57.PubMedGoogle Scholar
  84. Marshall JR (2001) Larry Clark's legacy: randomized controlled, selenium-based prostate cancer chemoprevention trials. Nutr Cancer 40(1): 74–77.PubMedGoogle Scholar
  85. Marshall JR, Sakr W, Wood D, et al. (2006) Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev 15(8): 1479–1484.PubMedGoogle Scholar
  86. McLeod DG, Srivastava S (2006) Androgen receptor mutation (T877A) promotes prostate cancer cell growth and cell survival. Oncogene 25(28): 3905–3913.PubMedGoogle Scholar
  87. Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19: 6550–6565.PubMedGoogle Scholar
  88. Menter DG, Sabichi AL, Lippman SM (2000) Selenium effects on prostate cell growth. Cancer Epidemiol Biomarkers Prev 9(11): 1171–1182.PubMedGoogle Scholar
  89. Meuillet E, Stratton S, Cherukuri DP, et al. (2004) Chemoprevention of prostate cancer with selenium: An update on current clinical trials and preclinical findings. J Cell Biochem 91: 443–458.PubMedGoogle Scholar
  90. Mohler JL, Gregory CW, Ford OHIII, et al. (2004) The androgen axis in recurrent prostate cancer. Clin Cancer Res 10(2): 440–448.PubMedGoogle Scholar
  91. Montgomery B, Mostaghel E, Vessella R, et al. (2007) Androgen synthesis in castration-adapted metastatic prostate cancer. ASCO Meeting 2007: Orlando, Florida, USA, 22–24 February (Abstract No. 98).Google Scholar
  92. Morris JD, Pramanik R, Zhang X, et al. (2006) 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(1): 111–122.PubMedGoogle Scholar
  93. Moscow JA, Schmidt L, Ingram DT, et al. (1994) Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. Carcinogenesis 15(12): 2769–2773.PubMedGoogle Scholar
  94. Navarro-Silvera SA, Rohan TE (2007) Trace elements and cancer risk: a review of the epidemiologic evidence. Cancer Causes Control 18: 7–27.PubMedGoogle Scholar
  95. Nieto M, Finn S, Loda M, et al. (2007) Prostate cancer: Re-focusing on androgen receptor signaling. The Intl J of Biochem Cell Biol 39: 1562–1568.Google Scholar
  96. Ni J, Chen M, Zhang Y, et al. (2003) Vitamin E succinate inhibits human prostate cancer cell growth via modulating cell cycle regulatory machinery. Biochem Biophys Res Commun 300(2): 357–363.PubMedGoogle Scholar
  97. Nomura AM, Lee J, Stemmermann GN, et al. (2000) Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 9: 883–887.PubMedGoogle Scholar
  98. Novoselov SV, Kryukov GV, Xu XM, et al. (2007) Selenoprotein H is a nuclear thioredoxin-like protein with a unique expression pattern. J Biol Chem 282(16): 11960–11968.PubMedGoogle Scholar
  99. Nyman DW, Stratton SM, Kopplin MJ, et al. (2004) Selenium and selenomethionine levels in prostate cancer patients. Cancer Detect Prev 28(1): 8–16.PubMedGoogle Scholar
  100. Ohta Y, Suzuki KT (2008) Methylation and demethylation of intermediates selenide and methylselenol in the metabolism of selenium. Toxicol. Appl. Pharmacol. 226(2): 169–177.PubMedGoogle Scholar
  101. Pak RW, Lanteri VJ, Scheuch JR, et al. (2002) Review of vitamin E and Selenium in the prevention of prostate cancer: implications of the selenium and vitamin E chemoprevention trial. Integr Cancer Ther 1(4): 338–344.PubMedGoogle Scholar
  102. Patrick L (2004) Selenium biochemistry and cancer: A review of the literature. Altern Med Rev 9(3): 239–258.PubMedGoogle Scholar
  103. Pienta KJ, Bradley D (2006) Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res 12(6): 1665–1671.PubMedGoogle Scholar
  104. Pinto JT, Sinha R, Papp K, et al. (2007) Differential effects of naturally occurring and synthetic organoselenium compounds on biomarkers in androgen responsive and androgen independent human prostate carcinoma cells. Int J Cancer 120: 1410–1417.PubMedGoogle Scholar
  105. Ramachandran K, Navarro L, Gordian E, et al. (2007) Methylation-mediated silencing of genes is not altered by selenium treatment of prostate cancer cells. AntiCancer Res 27(2): 921–925.PubMedGoogle Scholar
  106. Rayman MP (2000) The importance of selenium to human health. Lancet 356: 233–241.PubMedGoogle Scholar
  107. Ravn-Haren G, Bugel S, Krath BN, et al. (2007) A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: effects on oxidative defence regulation. Br J Nutr Sep 21, 1–10.Google Scholar
  108. Rayman MP (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc 64: 527–542.PubMedGoogle Scholar
  109. Rebsch CM, Penna FJ, Copeland PR (2006) Selenoprotein expression is regulated at multiple levels in prostate cells. Cell Res 16(12): 940–948.PubMedGoogle Scholar
  110. Reddy GP, Barrack ER, Dou QP, et al. (2006) Regulatory processes affecting androgen receptor expression, stability and function: potential targets to treat hormone-refractory prostate cancer. J Cell Biochem 98: 1408–1423.PubMedGoogle Scholar
  111. Reid ME, Stratton MS, Lillico A, et al. (2004) A report of high dose selenium supplementation: Response and toxicities. J Trace Elem Biol Med 18: 69–74.Google Scholar
  112. Ryan-Harshman M, Aldoori W (2005) The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Pract Res 66(2): 98–102.PubMedGoogle Scholar
  113. Sabichi AL, Lee JJ, Taylor RJ, et al. (2006) Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of L-selenomethionine: a Southwest Oncology Group study. Clin Cancer Res 12(7): 2178–2184.PubMedGoogle Scholar
  114. Scher HI, Sawyers CL (2005) Biology of progressive, castration-resistant prostate cancer: directed therapies targeting androgen receptor signaling axis. J Clin Oncol 23(32): 8253–8261.PubMedGoogle Scholar
  115. Schlicht M, Matysiak B, Brodzeller T, et al. (2004) Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium. BMC Genomics 5: 58–69.PubMedGoogle Scholar
  116. Schroder FH (2008) Progress in understanding androgen-independent prostate cancer (AIPC): A review of potential endocrine-mediated mechanisms. Eur Urol doi:10.1016/j.eururo. 2008.01.049.Google Scholar
  117. Schweizer L, Rizzo CA, Spires TE, et al. (2008) The androgen receptor can signal through Wnt/b-catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens. BMC Cell Biol 9:4.PubMedGoogle Scholar
  118. Schrauzer GN, White DA, Schneider CJ (1977a) Cancer mortality correlation studies-III: statistical associations with dietary selenium intakes. Bioinorganic Chem 7(1): 23–31.Google Scholar
  119. Schrauzer GN, White DA, Schneider CJ (1977b) Cancer mortality correlation studies-IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. Bioinorganic Chem 7(1): 35–56.Google Scholar
  120. Shamberger RJ, Frost DV (1969) Possible protective effect of selenium against human cancer. Can Med Assoc J 100(14): 682–692.PubMedGoogle Scholar
  121. Singh RP, Agarwal R (2006) Mechanisms of action of novel agents for prostate cancer chemoprevention. Endocr Related Cancer 13: 751–778.Google Scholar
  122. Sommer A, Haendler B (2003) Androgen receptor and prostate cancer: molecular aspects and gene expression profiling. Curr Opin Drug Discov Devel 6(5): 702–711.PubMedGoogle Scholar
  123. Spallholz JE (1994) On the nature of selenium toxicity and carcinostatic activity. Free Radic Biol Med 17: 45–64.PubMedGoogle Scholar
  124. Squires J, Berry MJ (2006) Selenium, Selenoproteins and cancer. Hawaii Med J 65(8): 239–240.PubMedGoogle Scholar
  125. Stanbrough M, Bubley GJ, Ross K, et al. (2006) Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 66: 2815–2825.PubMedGoogle Scholar
  126. Stratton MS, Reid ME, Schwartzberg G, et al. (2003a) Selenium and prevention of prostate cancer in high-risk men: the Negative Biopsy study. Anticancer Drugs 14(8): 589–594.Google Scholar
  127. Stratton MS, Reid ME, Schwartzberg G, et al. (2003b) Selenium and inhibition of disease progression in men diagnosed with prostate carcinoma: study design and baseline characteristics of the “Watchful Waiting” study. Anticancer Drugs 14(8): 595–600.Google Scholar
  128. Suh J, Rabson AB (2004) NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon? J Cell Biochem 91: 100–117.PubMedGoogle Scholar
  129. Syed DN, Khan N, Afaq F, et al. (2007) Chemoprevention of prostate cancer through dietary agents: Progress and promise. Cancer Epidemiol Biomarkers Prev 16(11): 2193–2203.PubMedGoogle Scholar
  130. Syed S, Tolcher A (2003) Innovative therapies for prostate cancer treatment. Rev Urol 5 (suppl 3): S78–84.PubMedGoogle Scholar
  131. Takaha N, Resar LM, Vindivich D, et al. (2004) High mobility group protein HMGI(Y) enhances tumor cell growth, invasion and matrix metalloproteinase-2 expression in prostate cancer cells. Prostate 60: 160–167.PubMedGoogle Scholar
  132. Taplin M-E (2007) Drug insight: role of the androgen receptor in the development and progression of prostate cancer. Nature Clin Pract Oncol 4(4): 236–244.Google Scholar
  133. Taplin ME, Rajeshkumar B, Halabi S, et al. (2003) Androgen receptor mutations in androgen-independent prostate cancer: Cancer and leukemia group study 1993. J Clin Oncol 21: 2673–2678.PubMedGoogle Scholar
  134. Terry S, Yang X, Chen MW, et al. (2006) Multifaceted interaction between the androgen receptor and Wnt signaling pathways and the implication for prostate cancer. J Cell Biochem 99: 402–410.PubMedGoogle Scholar
  135. Thompson IM (2007) Chemoprevention of prostate cancer: Agents and study designs. J Urol 178(3): S9–S13.PubMedGoogle Scholar
  136. Thomson CD, Robinson MF, Butler JA, et al. (1993) Long term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC in blood components of New Zealand women. Br J Nutr 69: 577–588.PubMedGoogle Scholar
  137. Titus MA, Schell MJ, Lih FB, et al. (2005) Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 11(13): 4653–4657.PubMedGoogle Scholar
  138. Ueda T, Bruchovsky N, Sadar MD (2002) Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and Stat3 signal transduction pathways. J Biol Chem 277: 7076–7085.PubMedGoogle Scholar
  139. Unni E, Sun S, Nan B, et al. (2004) Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence. Cancer Res 64: 7156–7168.PubMedGoogle Scholar
  140. Uzgare AR, Kapaln PJ, Greenberg NM (2003) Differential expression and/or activation of p38MAPK, erk1/2, and jnk in the initiation and progression of prostate cancer. Prostate 55: 128–139.PubMedGoogle Scholar
  141. Vadgama JV, Wu Y, Shen D, et al. (2000) Effect of selenium in combination with adriamycin or taxol on several different cancer cells. Anticancer Res 20(3A): 1391–1414.PubMedGoogle Scholar
  142. van den Brandt PA, Zeegers MP, Bode P, et al. (2003) Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev 12: 866–871.PubMedGoogle Scholar
  143. Vander Griend DJ, Litvinov IV, Isaacs JT (2007) Stabilizing androgen receptor in mitosis inhibits prostate cancer proliferation. Cell Cycle 6(6): 647–651.PubMedGoogle Scholar
  144. Venkateswaran V, Fleshner NE, Sugar LM, et al. (2004) Antioxidants block prostate cancer in Lady transgenic mice. Cancer Res 64(16): 5891–5896.PubMedGoogle Scholar
  145. Vogt TM, Ziegler RG, Patterson BH, et al. (2007) Racial differences in serum selenium concentration: Analysis of US population data from the Third National Health and Nutrition Examination survey. Am J Epidemiol 166(3): 280–288.PubMedGoogle Scholar
  146. Wang Z, Jiang C, Lu J (2002) Induction of caspase-mediated apoptosis and cell-cycle G1 arrest by selenium metabolite methylselenol. Mol Carcinog 34(3): 113–120.PubMedGoogle Scholar
  147. Wang Z, Hu H, Li G, et al. (2008) Methylseleninic acid inhibits microvascular endothelial G(1) cell cycle progression and decreases tumor microvessel density. Int J Cancer 122: 15–24.PubMedGoogle Scholar
  148. Waters DJ, Shen S, Cooley DM, et al. (2003) Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate. J Natl Cancer Inst 95(3): 237–241.PubMedGoogle Scholar
  149. Whanger PD (2002) Selenocompounds in plants and animals their biological significance. J Am Coll Nutr 21: 223–232.PubMedGoogle Scholar
  150. Whanger P, Vendeland S, Park YC, et al. (1996) Metabolism of subtoxic levels of selenium in animals and humans. Ann Clin Lab Sci 26: 99–113.PubMedGoogle Scholar
  151. World Health Organization. (1987) Selenium, Geneva World Health Organization, Environmental Health Criteria 58.Google Scholar
  152. Wu Y, Zhang H, Dong Y, et al. (2005) Endoplasmic reticulum stress signal mediators are targets of selenium action. Cancer Res 65(19): 9073–9079.PubMedGoogle Scholar
  153. Xia Y, Hill KE, Byrne DW, et al. (2005) Effectiveness of selenium supplements in a low selenium area of China. Am J Clin Nutr 81: 829–834.PubMedGoogle Scholar
  154. Yang SZ and Abdulkadir SA (2003) Early growth response gene 1 modulates androgen receptor signaling in prostate carcinoma cells. J Biol Chem 278(41): 39906–39911.PubMedGoogle Scholar
  155. Yang L, Wang L, Lin HK, et al. (2003) Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, Stat3 and MAPK, three distinct signal pathways in prostate cancer cells. Biochem Biophys Res Commun 305: 462–465.PubMedGoogle Scholar
  156. Yang X, Chen MW, Terry S, et al. (2006) Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells. Oncogene 25: 3436–3444.PubMedGoogle Scholar
  157. Yoshizawa K, Willett WC, Morris SJ, et al. (1998) Study of prediagnostic selenium levels in toenails and the risk of prostate cancer. J Natl Cancer Inst 90:1219–1224.PubMedGoogle Scholar
  158. Yu SY, Chu YJ, Li WG (1988) Selenium chemoprevention of liver cancer in animals and possible human applications. Biol Trace Elem Res 15: 231–241.PubMedGoogle Scholar
  159. Yu YP, Yu G, Tseng G, et al. (2007) Glutathione peroxidase 3, deleted or methylated in prostate cancer, suppresses prostate cancer growth and metastasis. Cancer Res 67(17): 8043–8050.PubMedGoogle Scholar
  160. Zachara BA, Szewczyk-Golec K, Tyloch J, et al. (2005a) Blood and tissue selenium concentrations and glutathione peroxidase activities in patients with prostate cancer and benign prostate hyperplasia. Neoplasma 52(3): 248–254.Google Scholar
  161. Zachara BA, Szewczyk-Golec K, Wolski Z, et al. (2005b) Selenium level in benign and cancerous prostate. Biol Trace Elem Res 103(3): 199–206.Google Scholar
  162. Zhao H and Brooks JD (2007) Selenomethionine induced transcriptional programs in human prostate cancer cells. J Urol 177: 743–750.PubMedGoogle Scholar
  163. Zhao H, Whitfield ML, Xu T, et al. (2004) Diverse effects of methylseleninic acid on the transcriptional program of human prostate cancer cells. Mol Biol Cell 15(2): 506–519.PubMedGoogle Scholar
  164. Zhao R, Domann FE, Zhong W (2006) Apoptosis induced by selenomethionine and methioninase is superoxide mediated and p53 dependent in human prostate cancer cells. Mol Cancer Ther 5(1): 3275–3284.PubMedGoogle Scholar
  165. Zu K, Ip C (2003) Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. Cancer Res 63(20): 6988–6995.PubMedGoogle Scholar
  166. Zu K, Bihani T, Lin A, et al. (2006) Enhanced selenium effect on growth arrest by BiP/GRP78 knockdown in p53-null human prostate cancer cells. Oncogene 25(4): 546–554.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Urology and Cancer CenterResearch III Bldg2nd AvenueUSA

Personalised recommendations