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

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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. This study aimed to examine the expression of PPAR-γ in human prostate cancer and the effect of PPAR-y ligands on prostate cancer cell growth. PPAR-γ is frequently overexpressed in androgen independent prostate cancer cell lines and human prostate cancer tissues (22 of 47 ; 47%). The effect of two PPAR-γ ligands, 15 deoxy-deltal2, 14 prostaglandin J2 (15d-PGJ2) and troglitazone, on the growth of a prostate cancer cell line was assessed. 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. PSA promoter reporter assays showed that troglitazone and 15d-PGJ2 down-regulated androgen stimulated reporter gene activity in LNCaP. The PSA promoter contains eight androgen receptor response elements. Interestingly, LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression. Taken together, these results suggest that PPAR-γ ligands may be a useful therapeutic agent for the treatment of prostate cancer.