Abstract

Prostate cancer is the most commonly diagnosed non-skin cancer in men and the second leading cause of cancer death in the United States. Prostate cancer, like many cancers, is a disease that generally requires a long period of time to develop and grow before it becomes detectable. This long period of latency makes prostate cancer a candidate for dietary chemoprevention. Soy and selenium (Se), are associated with a decreased risk of prostate cancer. We previously showed that high dietary intake of selenium (Se) and soy isoflavones decreased the expression of the androgen receptor (AR) and AR-regulated genes in the prostates of healthy rats. In this study we hypothesized that the downregulation of AR and AR-regulated genes would inhibit tumorigenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse. Mice were fed one of two stock diets with or without a supplement of Se in a 2 X 2 factorial design. The stock diets provided high or low dietary isoflavones. Mice were exposed to the diets from conception and sacrificed at 18 or 24 weeks of age. Prostate histopathology, urogenital tract (UGT) weight, serum IGF-1 levels, and the expression of AR and AR-regulated genes in the dorsolateral prostate was examined using quantitative PCR and Western blotting. Urogenital tract (UGT) weight was reduced compared to control in all dietary groups containing high Se, isoflavones, or both at 24 weeks (p<0.005). Dietary isoflavones delayed tumor progression and downregulated protein levels of AR, AR-regulated genes, and upregulated the protective FOXO1 and FOXO3a transcription factors. High dietary isoflavones also decreased the phosphorylation of the IGF-1R. The only main effect of Se was the upregulation of AKR1C14 the enzyme that deactivates 5&aplha;-DHT.This study identifies a previously unknown effect of isoflavones in the upregulation of FOXO expression and confirms previous studies of isoflavones' anticancer effects. Further research is needed to find a protective dose or form of Se and to elucidate the mechanism of isoflavones.

Degree

College and Department

Life Sciences; Nutrition, Dietetics, and Food Science

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