Combination effects of dietary soy and methylselenocysteine in a mouse model of prostate cancer
Menée sur un modèle murin transgénique d'adénocarcinome de la prostate, cette étude évalue les effets combinés de la consommation de soja et d'une supplémentation en méthylsélénocystéine sur la tumorigenèse et identifie les mécanismes associés
BACKGROUND: High dietary intake of soy or selenium (Se) is associated with decreased risk of prostate cancer. Soy constituents and various chemical forms of Se have each been shown to downregulate expression of the androgen receptor (AR) and AR-regulated genes in the prostate. We hypothesized that downregulation of AR and AR-regulated genes by the combination of these dietary components would inhibit tumorigenesis in the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mouse. METHODS: Male mice were exposed from conception to stock diets high or low in soy, with or without a supplement of Se-methylseleno-L-cysteine (MSC) in a 2 x 2 factorial design. Mice were sacrificed at 18 weeks. Prostate histopathology, urogenital tract (UGT) weight, hepatic activity of androgen-metabolizing enzymes, and expression of AR, AR-regulated, and AR-associated FOX family genes, in the dorsolateral prostate were examined. RESULTS: High soy intake decreased activity of hepatic aromatase and 5alpha-reductase, expression of AR, AR-regulated genes, FOXA1, UGT weight, and tumor progression, and upregulated protective FOXO3. Supplemental MSC upregulated AKR1C14, which reduces 5alpha-dihydrotestosterone. CONCLUSIONS: Soy is an effective pleiotropic dietary agent for prevention of prostate cancer. The finding of effects of soy on FOX family gene expression in animals is novel. Combination effects of supplemental MSC may depend upon the soy content of the basal diet to which it is added. Prostate (c) 2013 Wiley Periodicals, Inc.