Abstract
BackgroundHigh dietary intake of selenium or soybean isoflavones reduces prostate cancer risk. These components each affect androgen-regulated gene expression. The objective of this work was to determine the combined effects of selenium and isoflavones on androgen-regulated gene expression in rat prostate.MethodsMale Noble rats were exposed from conception until 200 days of age to diets containing an adequate (0.33-0.45 mg/kg diet) or high (3.33-3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 × 2 factorial design. Gene expression in the dorsolateral prostate was determined for the androgen receptor, for androgen-regulated genes, and for Akr1c9, whose product catalyzes the reduction of dihydrotestosterone to 5alpha-androstane-3alpha, 17beta-diol. Activity of hepatic glutathione peroxidise 1 and of prostatic 5alpha reductase were also assayed.ResultsThere were no differences due to diet in activity of liver glutathione peroxidase activity. Total activity of 5alpha reductase in prostate was significantly lower (p = 0.007) in rats fed high selenium/high isoflavones than in rats consuming adequate selenium/low isoflavones. High selenium intake reduced expression of the androgen receptor, Dhcr24 (24-dehydrocholesterol reductase), and Abcc4 (ATP-binding cassette sub-family C member 4). High isoflavone intake decreased expression of Facl3 (fatty acid CoA ligase 3), Gucy1a3 (guanylate cyclase alpha 3), and Akr1c9. For Abcc4 the combination of high selenium/high isoflavones had a greater inhibitory effect than either treatment alone. The effects of selenium on gene expression were always in the direction of chemopreventionConclusionThese results suggest that combined intake of high selenium and high isoflavones may achieve a greater chemopreventive effect than either compound supplemented individually.
Highlights
High dietary intake of selenium or soybean isoflavones reduces prostate cancer risk
In addition to the four androgen receptor (AR)- and Se-regulated genes relevant in prostate cancer, for which homologs exist in rats, we examined expression of the AR itself and of Akr1c9 – the gene for the enzyme which catalyzes the reduction of dihydrotestosterone to its corresponding, less potent 5alpha-androstane-3alpha, 17beta-diol
Isoflavone analysis As expected, serum isoflavone levels were significantly higher in rats fed the high isoflavone diets
Summary
High dietary intake of selenium or soybean isoflavones reduces prostate cancer risk. These components each affect androgen-regulated gene expression. The objective of this work was to determine the combined effects of selenium and isoflavones on androgen-regulated gene expression in rat prostate. The American Cancer Society estimates that there will be about 186,320 new cases of prostate cancer in the United States in 2008. The Nutritional Prevention of Cancer Trial showed a significant reduction in prostate cancer incidence in men receiving a daily supplement of 200 μg selenium (Se) as selenized yeast [2,3]. Chan et al [4], in their review of diet in the development and progression of prostate cancer, found the evidence more convincing for a protective effect of Se than for any other dietary component.
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