Surgery (St Vincent's) - Research Publications

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Author: Thompson, Erik × Author: CHAFFER, CHRISTINE × Start date: 2004 × End date: 2009 ×

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    PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma
    Chaffer, CL ; Thomas, DM ; Thompson, EW ; Williams, ED (BMC, 2006-03-06)
    BACKGROUND: Although PPARgamma antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARgamma ligands induce PPARgamma-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 PPARgamma 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 J2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARgamma 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 PPARgamma-independent.