The Nutritional Prevention of Cancer Trial showed that selenium supplementation reduced the incidence of prostate cancer by approximately 50%.Our study demonstrated a novel mechanism of selenium anticancer action.We found that selenium, in the form of methylseleninic acid, markedly inhibited androgen receptor (AR) expression and transactivation in both androgen-dependent and androgen-independent human prostate cancer cells.The suppression of AR signaling occurred well before growth inhibition became evident.In addition, restoration of AR significantly weakened the inhibitory effect of selenium on cell growth and proliferation.The findings therefore indicated a key role of AR-signaling suppression in mediating the anticancer effect of selenium in prostate cancer.