contentLife Extension Magazine December 2013 New Study Reveals Four Nutrients that Lower PSA and Slow Cancer Progression By Ramon Gonzales References Bastian PJ, Boorjian SA, Bossi A, et al. High-risk prostate cancer: from definition to contemporary management. Eur Urol. 2012 Jun;61(6):1096-106. Available at: http://www.cdc.gov/cancer/prostate/statistics/. Accessed September 17, 2013. Loeb S, Berglund A, Stattin P. Population based study of use and determinants of active surveillance and watchful waiting for low and intermediate risk prostate cancer. J Urol. 2013 May 30. Bul M, van den Bergh RC, Zhu X, et al. Outcomes of initially expectantly managed patients with low or intermediate risk screen-detected localized prostate cancer. BJU Int. 2012 Dec;110(11):1672-7. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. Summary of the National Cancer Research Network double-blind placebo controlled randomised trial. J Clin Oncol. 2013;31(Suppl; abs 5008). Faria A, Monteiro R, Azevedo I, Calhau C. Pomegranate juice effects on cytochrome P450S expression: in vivo studies. J Med Food. 2007 Dec;10(4):643-9. Saruwatari A, Okamura S, Nakajima Y, Narukawa Y, Takeda T, Tamura H. Pomegranate juice inhibits sulfoconjugation in Caco-2 human colon carcinoma cells. J Med Food. 2008 Dec;11(4):623-8. Vicinanza R, Zhang Y, Henning SM, Heber D. Pomegranate juice metabolites, ellagic acid and urolithin A, synergistically inhibit androgen-independent prostate cancer cell growth via distinct effects on cell cycle control and apoptosis. Evid Based Complement Alternat Med. 2013;2013:247504. Sineh Sepehr K, Baradaran B, Mazandarani M, Khori V, Shahneh FZ. Studies on the cytotoxic activities of Punica granatum L. var. spinosa (apple punice) extract on prostate cell line by induction of apoptosis. ISRN Pharm. 2012;2012:547942. Lee ST, Wu YL, Chien LH, Chen ST, Tzeng YK, Wu TF. Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell. Proteomics. 2012 Nov;12(21):3251-62. Gasmi J, Sanderson JT. Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells. J Agric Food Chem. 2010 Nov 10. Adhami VM, Khan N, Mukhtar H. Cancer chemoprevention by pomegranate: laboratory and clinical evidence. Nutr Cancer. 2009;61(6):811-5. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006 Jul 1;12(13):4018-26. Malik A, Mukhtar H. Prostate cancer prevention through pomegranate fruit. Cell Cycle. 2006 Feb;5(4):371-3. Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14813-8. Albrecht M, Jiang W, Kumi-Diaka J, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004 Fall;7(3):274-83. Hong MY, Seeram NP, Heber D. Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor. J Nutr Biochem. 2008 Dec;19(12):848-55. Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013 Mar;16(1):50-5. Seeram NP, Aronson WJ, Zhang Y, et al. Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J Agric Food Chem. 2007 Sep 19;55(19):7732-7. Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model. Carcinogenesis. 2012 Mar;33(3):644-51. Selvi BR, Batta K, Kishore AH, et al. Identification of a novel inhibitor of coactivator-associated arginine methyltransferase 1 (CARM1)-mediated methylation of histone H3 Arg-17. J Biol Chem. 2010 Mar 5;285(10):7143-52. Sartippour MR, Seeram NP, Rao JY, et al. Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo. Int J Oncol. 2008 Feb;32(2):475-80. Wang L, Ho J, Glackin C, Martins-Green M. Specific pomegranate juice components as potential inhibitors of prostate cancer metastasis. Transl Oncol. 2012 Oct;5(5):344-55. Pitchakarn P, Chewonarin T, Ogawa K, et al. Ellagic Acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac J Cancer Prev. 2013;14(5):2859-63. Connors SK, Chornokur G, Kumar NB. New insights into the mechanisms of green tea catechins in the chemoprevention of prostate cancer. Nutr Cancer. 2012;64(1):4-22. McCarthy S, Caporali A, Enkemann S, et al. Green tea catechins suppress the DNA synthesis marker MCM7 in the TRAMP model of prostate cancer. Mol Oncol. 2007 Sep;1(2):196-204. O’Sullivan J, Sheridan J, Mulcahy H, Tenniswood M, Morrissey C. The effect of green tea on oxidative damage and tumour formation in Lobund-Wistar rats. Eur J Cancer Prev. 2008 Nov;17(6):489-501. Pezzato E, Sartor L, Dell’Aica I, 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. 2004 Dec 10;112(5):787-92. Henning SM, Aronson W, Niu Y, et al. Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption. J Nutr. 2006 Jul;136(7): 1839-43. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. 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. 2006 Jan 15;66(2):1234-40. Pandey M, Gupta S. Green tea and prostate cancer: from bench to clinic. Front Biosci (Elite Ed). 2009;1:13-25. McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila). 2009 Jul;2(7):673-82. Siddiqui IA, Zaman N, Aziz MH, et al. Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas. Carcinogenesis. 2006 Apr;27(4):833-9. Chuu CP, Chen RY, Kokontis JM, Hiipakka RA, Liao S. Suppression of androgen receptor signaling and prostate specific antigen expression by (-)-epigallocatechin-3-gallate in different progression stages of LNCaP prostate cancer cells. Cancer Lett. 2009 Mar 8;275(1):86-92. Fujiki H, Suganuma M. Green tea: an effective synergist with anticancer drugs for tertiary cancer prevention. Cancer Lett. 2012 Nov 28;324(2):119-25. Jian L, Lee AH, Binns CW. Tea and lycopene protect against prostate cancer. Asia Pac J Clin Nutr. 2007;16 Suppl 1:453-7. Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 2008 Jan 1;167(1):71-7. Harper CE, Patel BB, Wang J, Eltoum IA, Lamartiniere CA. Epigallocatechin-3-Gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: mechanisms of action. Prostate. 2007 Oct 1;67(14):1576-89. Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. Faseb j. 2011 Apr;25(4):1198-207. Lee YH, Kwak J, Choi HK, et al. EGCG suppresses prostate cancer cell growth modulating acetylation of androgen receptor by anti-histone acetyltransferase activity. Int J Mol Med. 2012 Jul;30(1):69-74. Gupta K, Thakur VS, Bhaskaran N, et al. Green tea polyphenols induce p53-dependent and p53-independent apoptosis in prostate cancer cells through two distinct mechanisms. PLoS One. 2012;7(12):e52572. Hagen RM, Chedea VS, Mintoff CP, Bowler E, Morse HR, Ladomery MR. Epigallocatechin-3-gallate promotes apoptosis and expression of the caspase 9a splice variant in PC3 prostate cancer cells. Int J Oncol. 2013 Jul;43(1):194-200. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001 Jun 1;47(4):293-303. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. Aaps j. 2013 Jan;15(1):195-218. Rao KV, Samikkannu T, Dakshayani KB, et al. Chemopreventive potential of an ethyl acetate fraction from Curcuma longa is associated with upregulation of p57(kip2) and Rad9 in the PC-3M prostate cancer cell line. Asian Pac J Cancer Prev. 2012;13(3): 1031-8. Cheng TS, Chen WC, Lin YY, et al. Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prev Res (Phila). 2013 May;6(5):495-505. Killian PH, Kronski E, Michalik KM, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Carcinogenesis. 2012 Dec;33(12):2507-19. Sundram V, Chauhan SC, Ebeling M, Jaggi M. Curcumin attenuates beta-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS One. 2012;7(4):e35368. Herman JG, Stadelman HL, Roselli CE. Curcumin blocks CCL2-induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity. Int J Oncol. 2009 May;34(5):1319-27. Yang L, Zhang LY, Chen WW, et al. Inhibition of the expression of prostate specific antigen by curcumin. Yao Xue Xue Bao. 2005 Sep;40(9):800-3. Chung LC, Tsui KH, Feng TH, Lee SL, Chang PL, Juang HH. Curcumin provides potential protection against the activation of hypoxia and prolyl 4-hydroxylase inhibitors on prostate-specific antigen expression in human prostate carcinoma cells. Mol Nutr Food Res. 2011 Nov;55(11):1666-76. Tsui KH, Feng TH, Lin CM, Chang PL, Juang HH. Curcumin blocks the activation of androgen and interlukin-6 on prostate-specific antigen expression in human prostatic carcinoma cells. J Androl. 2008 Nov-Dec;29(6):661-8. Choi HY, Lim JE, Hong JH. Curcumin interrupts the interaction between the androgen receptor and Wnt/beta-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis. 2010 Dec;13(4):343-9. Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res. 2013 Jul 12. Teiten MH, Gaascht F, Cronauer M, Henry E, Dicato M, Diederich M. Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol. 2011 Mar;38(3):603-11. Guo H, Xu YM, Ye ZQ, Yu JH, Hu XY. Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor. Pharmazie. 2013 Jun;68(6):431-4. Shankar S, Ganapathy S, Chen Q, Srivastava RK. Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol Cancer. 2008;7:16. Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene. 2004 Feb 26;23(8):1599-607. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62(7):919-30. Hung CM, Su YH, Lin HY, et al. Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. J Agric Food Chem. 2012 Aug 16. Shah S, Prasad S, Knudsen KE. Targeting pioneering factor and hormone receptor cooperative pathways to suppress tumor progression. Cancer Res. 2012 Mar 1;72(5):1248-59. Teiten MH, Gaigneaux A, Chateauvieux S, et al. Identification of differentially expressed proteins in curcumin-treated prostate cancer cell lines. Omics. 2012 Jun;16(6):289-300. Clarke JD, Hsu A, Yu Z, Dashwood RH, Ho E. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res. 2011 Jul;55(7):999-1009. Rogan EG. The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo. 2006 Mar-Apr;20(2):221-8. Joseph MA, Moysich KB, Freudenheim JL, et al. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer. 2004;50(2):206-13. Abdull Razis AF, Noor NM. Cruciferous vegetables: dietary phytochemicals for cancer prevention. Asian Pac J Cancer Prev. 2013;14(3):1565-70. Dashwood RH, Ho E. Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007 Oct;17(5):363-9. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood). 2007 Feb;232(2):227-34. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. Faseb j. 2006 Mar;20(3):506-8. Gryder BE, Rood MK, Johnson KA, et al. Histone deacetylase inhibitors equipped with estrogen receptor modulation activity. J Med Chem. 2013 Jul 3. Stettner M, Kramer G, Strauss A, et al. Long-term antiepileptic treatment with histone deacetylase inhibitors may reduce the risk of prostate cancer. Eur J Cancer Prev. 2012 Jan;21(1):55-64. Kirsh VA, Peters U, Mayne ST, et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst. 2007 Aug 1;99(15):1200-9. Canene-Adams K, Lindshield BL, Wang S, Jeffery EH, Clinton SK, Erdman JW, Jr. Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas. Cancer Res. 2007 Jan 15;67(2):836-43. Zhang J, Hsu BAJ, Kinseth BAM, Bjeldanes LF, Firestone GL. Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells. Cancer. 2003 Dec 1;98(11):2511-20. Chiao JW, Chung FL, Kancherla R, Ahmed T, Mittelman A, Conaway CC. Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int J Oncol. 2002 Mar;20(3):631-6. Han HY, Shan S, Zhang X, Wang NL, Lu XP, Yao XS. Down-regulation of prostate specific antigen in LNCaP cells by flavonoids from the pollen of Brassica napus L. Phytomedicine. 2007 May;14(5):338-43. Traka MH, Spinks CA, Doleman JF, et al. The dietary isothiocyanate sulforaphane modulates gene expression and alternative gene splicing in a PTEN null preclinical murine model of prostate cancer. Mol Cancer. 2010;9:189. Melchini A, Traka MH, Catania S, et al. Antiproliferative activity of the dietary isothiocyanate erucin, a bioactive compound from cruciferous vegetables, on human prostate cancer cells. Nutr Cancer. 2013;65(1):132-8. Hahm ER, Singh SV. Sulforaphane inhibits constitutive and interleukin-6-induced activation of signal transducer and activator of transcription 3 in prostate cancer cells. Cancer Prev Res (Phila). 2010 Apr;3(4):484-94. Choi S, Singh SV. Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent. Cancer Res. 2005 Mar 1;65(5):2035-43. Ho E, Clarke JD, Dashwood RH. Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention. J Nutr. 2009 Dec;139(12):2393-6. Traka M, Gasper AV, Melchini A, et al. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS One. 2008;3(7):e2568. Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database Syst Rev. 2013;1:Cd004720. Van Neste L, Herman JG, Otto G, Bigley JW, Epstein JI, Van Criekinge W. The epigenetic promise for prostate cancer diagnosis. Prostate. 2012 Aug 1;72(11):1248-61. Benchikh El Fegoun A, Villers A, Moreau JL, Richaud P, Rebillard X, Beuzeboc P. PSA and follow-up after treatment of prostate cancer. Prog Urol. 2008 Mar;18(3):137-44.