PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma

Background: Although PPAR. antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPAR gamma ligands induce PPAR gamma-independent effects. There is a need to better define such effects to permit rational utilization of these agents. Methods: We have studied the effects of a range of endogenous and synthetic PPAR gamma ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2). Results: 15-deoxy-prostaglandin J(2) (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPAR. antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis. Conclusion: Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPAR gamma-independent.