RESEARCH
Year : 2007  |  Volume : 6  |  Issue : 1  |  Page : 3

Genistein chemoprevention of prostate cancer in TRAMP mice


1 Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA
2 Department of Pathology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
3 Department of Pharmacology and Toxicology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence Address:
Coral A Lamartiniere
Department of Pharmacology and Toxicology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.1186/1477-3163-6-3

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 Tr ansgenic a denocarcinoma m ouse p rostate (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.


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