EHPnet: WHO/AFRO Division of Healthy Environments and Sustainable Development

Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. Genistein, the predominant phytoestrogen in soy food, has been proposed as a potential chemopreventive agent due to its anti-estrogen and tyrosine kinase inhibitory effects. To determine the most effective period for genistein chemoprevention, the Transgenic adenocarcinoma mouse prostate (TRAMP) model was used. The treatments were 250 mg genistein/kg AIN-76A diet 1) prepubertally only, 2) in adulthood only or 3) through out life. Controls received AIN-76A diet. By 28 weeks of age, 100% TRAMP mice fed control diet developed prostatic intraepithelial neoplasia (PIN) or adenocarcinomas with 6%, 16%, 44% and 34% developing high grade PIN, well differentiated, moderately differentiated and poorly differentiated prostatic adenocarcinomas, respectively. Prepubertal only (1–35 days postpartum) and adult only genistein treatments (12 – 28 weeks) resulted in 6% and 29% decreases in poorly-differentiated cancerous lesions compared with controls, respectively. The most significant effect was seen in the TRAMP mice exposed to genistein throughout life (1–28 weeks) with a 50% decrease in poorly-differentiated cancerous lesions. In a separate experiment in castrated TRAMP mice, dietary genistein suppressed the development of advanced prostate cancer by 35% compared with controls. Of the tumors that developed in castrated TRAMP mice, 100% were poorly-differentiated in contrast to the 37% of noncastrated TRAMP mice that developed poorly-differentiated tumors. ICI 182,780 (ICI), genistein and estrogen down-regulated androgen receptor (AR), estrogen receptor alpha (ER-α) and progesterone receptor (PR) in the prostates of C57BL/6 mice, and act independently of ER. Our data obtained in intact and castrated transgenic mice suggest that genistein may be a promising chemopreventive agent against androgen-dependent and independent prostate cancers. Background Prostate cancer is the most frequently diagnosed cancer in North American men and accounts for the second largest number of male cancer deaths in the United States [1]. Clinically manifested prostate cancer is less prevalent among Asian men where the intake of soy products is high [2-4]. However, Asians who immigrate to the United States and adopt a Western diet lose this protection [5-8]. High consumption of food containing soy results in high plasma, urine, and prostatic fluid concentrations of phytoestrogens [9,10]. Genistein, the most abundant phytoestrogen component of soy, has been shown to inhibit the growth of both androgen-dependent and independent [11,12] prostate cancer cells. Prostate tumor incidence is Published: 16 March 2007 Journal of Carcinogenesis 2007, 6:3 doi:10.1186/1477-3163-6-3 Received: 19 May 2006 Accepted: 16 March 2007 This article is available from: http://www.carcinogenesis.com/content/6/1/3 © 2007 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.