Monomethylated selenium inhibits growth of LNCaP human prostate cancer xenograft accompanied by a decrease in the expression of androgen receptor and prostate-specific antigen (PSA).

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Objectives. Epidemiological studies and prevention trials suggest selenium is a promising preventive agent for prostate cancer. Selenium containing compounds inhibited the growth of prostate cancer cell lines including androgen sensitive LNCaP and androgen insensitive DU145 and PC3 cells in vitro. Previous study revealed a novel mechanism of selenium action in which selenium (methylseleninic acid) markedly reduced androgen receptor signaling in prostate cancer cells, suggesting that selenium might act as an anti-androgen, which could serve as a therapeutic agent for prostate cancer. In this study, we tested whether selenium (methylselenocysteine) affects tumor growth of human prostate cancer cells by targeting androgen receptor signaling in vivo. Methods. Prostate tumor xenografts were established in nude mice by co-inoculating LNCaP cells with Matrigel. The mice bearing tumors were treated with or without methylselenocysteine (100 μg/mouse/day) via intraperitoneal injection for 2 weeks. The effect of methylselenocysteine on tumor growth, androgen receptor and prostate-specific antigen (PSA) expression was examined. Results. Methylselenocysteine significantly inhibited LNCaP tumor growth (p< 0.05). Androgen receptor expression in tumor tissues and serum PSA levels were considerably decreased in methylselenocysteine treated mice compared to the vehicle controls. Conclusions. Pharmacological dose of methylselenocysteine inhibits the growth of LNCaP human prostate cancer in vivo accompanied by a decrease in the expression of androgen receptor and PSA. These findings suggest that selenium (methylselenocysteine) can serve as a therapeutic agent aimed at disruption of AR signaling for prostate cancer.