The PPAR&[gamma] Inhibitor GW9662 Attenuates Phenylbutyrate-Induced Lipid Metabolite Accumulation in DU145 Prostate Cancer Cells
Milkevitch M, Beardsley N, Delikatny E
University of PA School of Medicine
1H and 31P MRS were used to monitor the effects of the peroxisome proliferator activated receptor &[gamma](PPAR&[gamma])antagonist GW9662 on prostate cells treated with the differentiating agent phenylbutyrate. Phenylbutyrate (PB) causes G1 cell cycle arrest and apoptosis in DU145 cells, along with significant increases in total choline and mobile lipid resonances in 1H spectra and glycerophosphocholine in 31P spectra. Pretreatment of DU145 cells with GW9662 (1&[mu]M, 1h)completely inhibited PB induced effects on lipid metabolites and reversed the G1 block. These data provide strong evidence that PB-induced differentiation and lipid metabolic changes are mediated by PPAR&[gamma].