Anti-proliferative effect of a triazole derivative (ST1959) on LNCaP human prostate cancer cells through down-regulation of cyclin and androgen receptor expression.

BACKGROUND. Previous studies demonstrated that ST1959, a triazole derivative endowed with immunomodulatory activities, also exerts inhibitory effects on proliferation and survival of a panel of tumor cells. In this study, we sought to ascertain the effects of ST1959 on the growth of androgen-dependent and androgen-independent prostate cancer (PCa) cells. METHODS. The growth of androgen-dependent (LNCaP) and androgen-independent (PC3, DU-145) cells was analyzed in vitro both in the presence and absence of ST1959. Modulation of cyclin and androgen receptor (AR) expression following treatment with ST1959 was analyzed by Western blot and cytofluorimetric analysis. RESULTS. We observed that ST1959 causes a significant growth inhibition of LNCaP cells without affecting proliferation of androgen-insensitive DU-145 and PC3 cell lines. These effects were associated with G0/G1 cell cycle arrest and down-regulation of cyclin D1, A and B and AR expression. CONCLUSIONS. Our present findings indicate that the anti-proliferative activity of ST1959 on cell growth of androgen-dependent LNCaP PCa cells may be brought about by decreasing expression of functional AR and selected cyclins, ultimately leading to cell growth inhibition.