Peroxisome proliferator-activated receptor-γ and growth inhibition by its ligands in prostate cancer

Background: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is expressed in certain human cancers. Ligand-induced PPAR-γ activation can result in growth inhibition and differentiation in these cancer cells; however, the precise mechanism for the anti-proliferative effect of PPAR-γ ligands is not clear. Methods: In this study, we examined the expression of PPAR-γ in human prostate cancer and the effect of two PPAR-γ ligands, 15 deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and troglitazone, on prostate cancer cell growth. Results: PPAR-γ is frequently over-expressed in androgen independent prostate cancer cell lines and human prostate cancer tissues (22 of 47; 47%). Both 15d-PGJ2 and troglitazone inhibited proliferation and DNA synthesis of prostate cancer cell lines in a dose-dependent manner, and slightly increased the proportion of cells with S-phase DNA content. Prostate specific antigen (PSA) promoter reporter assays showed that troglitazone and 15d-PGJ2 down-regulated androgen stimulated reporter gene activity in prostate cancer cell lines LNCaP. Interestingly, LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression. Conclusions: Taken together, these results suggest that PPAR-γ ligands may be a useful therapeutic agent for the treatment of prostate cancer.