PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma
1 Bernard O'Brien Institute of Microsurgery, Victoria, Australia
2 Ian Potter Foundation Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, Victoria, Australia
3 The University of Melbourne Department of Surgery, St. Vincent's Hospital, Victoria, Australia
4 St Vincent's Institute of Medical Research, Victoria, Australia
BMC Cancer 2006, 6:53 doi:10.1186/1471-2407-6-53Published: 6 March 2006
Although PPARγ antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARγ ligands induce PPARγ-independent effects. There is a need to better define such effects to permit rational utilization of these agents.
We have studied the effects of a range of endogenous and synthetic PPARγ 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).
15-deoxy-prostaglandin J2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARγ 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.
Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARγ-independent.