Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial

Jill M Hamilton-Reeves, Snigdha Banerjee, Sushanta K Banerjee, Jeffrey M Holzbeierlein, J Brantley Thrasher, Suman Kambhampati, John Keighley, Peter Van Veldhuizen, Jill M Hamilton-Reeves, Snigdha Banerjee, Sushanta K Banerjee, Jeffrey M Holzbeierlein, J Brantley Thrasher, Suman Kambhampati, John Keighley, Peter Van Veldhuizen

Abstract

Purpose: We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer.

Methodology/principal findings: We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n=42) or placebo (n=44) for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM). Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant.

Conclusions/significance: These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA.

Trial registration: ClinicalTrials.gov NCT00255125.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Participant Flow Diagram.
Figure 1. Participant Flow Diagram.
Figure 2. Cell cycle gene array of…
Figure 2. Cell cycle gene array of the prostate tumor specimen obtained from two patients with prostate cancer, one who consumed isoflavones and one who took the placebo.
The figure shows the ratio of the gene to GAPDH.
Figure 3. Apoptosis gene array of the…
Figure 3. Apoptosis gene array of the prostate tumor specimen obtained from two patients with prostate cancer, one who consumed isoflavones and one who took the placebo.
The figure shows the ratio of the gene to GAPDH.

References

    1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62: 10–29.
    1. Yan L, Spitznagel EL (2009) Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. The American Journal of Clinical Nutrition 89: 1155–1163.
    1. Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM (2009) Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutrition and cancer 61: 598–606.
    1. Travis RC, Allen NE, Appleby PN, Price A, Kaaks R, et al. (2012) Prediagnostic concentrations of plasma genistein and prostate cancer risk in 1,605 men with prostate cancer and 1,697 matched control participants in EPIC. Cancer Causes Control 23: 1163–1171.
    1. Morton MS, Arisaka O, Miyake N, Morgan LD, Evans BA (2002) Phytoestrogen concentrations in serum from Japanese men and women over forty years of age. J Nutr 132: 3168–3171.
    1. Adlercreutz H, Markkanen H, Watanabe S (1993) Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342: 1209–1210.
    1. Messina M, Nagata C, Wu AH (2006) Estimated Asian adult soy protein and isoflavone intakes. Nutrition and cancer 55: 1–12.
    1. Marks LS, Kojima M, Demarzo A, Heber D, Bostwick DG, et al. (2004) Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue. Urology 64: 765–771.
    1. Whittemore AS, Wu AH, Kolonel LN, John EM, Gallagher RP, et al. (1995) Family history and prostate cancer risk in white and Asian men in the United States and Canada. American Journal of Epidemiology 141: 732–740.
    1. Gardner C, Oelrich B, Liu J, Feldman D, Franke A, et al. (2009) Prostatic soy isoflavone concentrations exceed serum levels after dietary supplementation. The Prostate 69: 719–726.
    1. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS (2007) Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr 137: 1769–1775.
    1. Hamilton-Reeves JM, Rebello SA, Thomas W, Slaton JW, Kurzer MS (2007) Soy protein isolate increases urinary estrogens and the ratio of 2:16alpha-hydroxyestrone in men at high risk of prostate cancer. J Nutr 137: 2258–2263.
    1. Handayani R, Rice L, Cui Y, Medrano TA, Samedi VG, et al. (2006) Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. J Nutr 136: 75–82.
    1. Li Y, Wang Z, Kong D, Li R, Sarkar SH, et al. (2008) Regulation of Akt/FOXO3a/GSK-3beta/AR signaling network by isoflavone in prostate cancer cells. J Biol Chem 283: 27707–27716.
    1. Jarred RA, Keikha M, Dowling C, McPherson SJ, Clare AM, et al. (2002) Induction of apoptosis in low to moderate-grade human prostate carcinoma by red clover-derived dietary isoflavones. Cancer Epidemiol Biomarkers Prev 11: 1689–1696.
    1. Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, et al. (2005) Intensive lifestyle changes may affect the progression of prostate cancer. Journal of Urology 174: 1065–1069.
    1. Dalais FS, Meliala A, Wattanapenpaiboon N, Frydenberg M, Suter DA, et al. (2004) Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urology 64: 510–515.
    1. Lazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, et al. (2011) Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind Phase 2 clinical trial. Nutr Cancer 63: 889–898.
    1. deVere White RW, Tsodikov A, Stapp EC, Soares SE, Fujii H, et al. (2010) Effects of a high dose, aglycone-rich soy extract on prostate-specific antigen and serum isoflavone concentrations in men with localized prostate cancer. Nutrition and cancer 62: 1036–1043.
    1. Hamilton-Reeves JM, Rebello SA, Thomas W, Kurzer MS, Slaton JW (2008) Effects of soy protein isolate consumption on prostate cancer biomarkers in men with HGPIN, ASAP, and low-grade prostate cancer. Nutr Cancer 60: 7–13.
    1. Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, et al. (2007) Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 85: 1148–1156.
    1. van Veldhuizen PJ, Thrasher JB, Ray G, Cherian R, Ward J, et al. (2006) Dose effect of soy supplementation in prostate cancer: a pilot study. Oncol Rep 16: 1221–1224.
    1. Setchell KD, Cole SJ (2006) Method of defining equol-producer status and its frequency among vegetarians. J Nutr 136: 2188–2193.
    1. Hamilton-Reeves JM, Vazquez G, Duval SJ, Phipps WR, Kurzer MS, et al. (2010) Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil Steril 94: 997–1007.
    1. Tanaka M, Fujimoto K, Chihara Y, Torimoto K, Yoneda T, et al. (2009) Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate cancer and prostatic diseases 12: 247–252.
    1. Miyanaga N, Akaza H, Hinotsu S, Fujioka T, Naito S, et al. (2012) Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci 103: 125–130.
    1. Kumar NB, Krischer JP, Allen K, Riccardi D, Besterman-Dahan K, et al. (2007) A Phase II randomized, placebo-controlled clinical trial of purified isoflavones in modulating steroid hormones in men diagnosed with localized prostate cancer. Nutrition and cancer 59: 163–168.
    1. Kumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, et al. (2004) The specific role of isoflavones in reducing prostate cancer risk. Prostate 59: 141–147.
    1. Kumar NB, Kang L, Pow-Sang J, Xu P, Allen K, et al. (2010) Results of a randomized phase I dose-finding trial of several doses of isoflavones in men with localized prostate cancer: administration prior to radical prostatectomy. Journal of the Society for Integrative Oncology 8: 3–13.
    1. Nagata C, Takatsuka N, Shimizu H, Hayashi H, Akamatsu T, et al. (2001) Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men. Cancer Epidemiol Biomarkers Prev 10: 179–184.
    1. Kranse R, Dagnelie PC, van Kemenade MC, de Jong FH, Blom JH, et al. (2005) Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study. Int J Cancer 113: 835–840.
    1. Kwan W, Duncan G, Van Patten C, Liu M, Lim J (2010) A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer. Nutrition and cancer 62: 198–207.
    1. Maskarinec G, Morimoto Y, Hebshi S, Sharma S, Franke AA, et al. (2006) Serum prostate-specific antigen but not testosterone levels decrease in a randomized soy intervention among men. Eur J Clin Nutr 60: 1423–1429.
    1. Grainger EM, Schwartz SJ, Wang S, Unlu NZ, Boileau TW, et al. (2008) A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen. Nutr Cancer 60: 145–154.
    1. Frankenfeld CL, Patterson RE, Horner NK, Neuhouser ML, Skor HE, et al. (2003) Validation of a soy food-frequency questionnaire and evaluation of correlates of plasma isoflavone concentrations in postmenopausal women. Am J Clin Nutr 77: 674–680.
    1. Franke AA, Custer LJ, Wilkens LR, Le Marchand LL, Nomura AM, et al. (2002) Liquid chromatographic-photodiode array mass spectrometric analysis of dietary phytoestrogens from human urine and blood. Journal of chromatographyB, Analytical technologies in the biomedical and life sciences 777: 45–59.
    1. Banerjee S, Dhar G, Haque I, Kambhampati S, Mehta S, et al. (2008) CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells. Cancer Res 68: 7606–7612.

Source: PubMed

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