Phenylbutyrate Induces Apoptosis and Lipid Accumulations via a Peroxisome Proliferator-Activated Receptor Gamma-Dependent Pathway

摘要

The effects of the selective peroxisome proliferator activated receptor-gamma (PPAR-γ) inhibitor GW9662 on phenylbutyrate (PB)-induced NMR-detectable lipid metabolites was investigated on DU145 prostate cancer cells. DU145 cells were perfused with 10 mM PB in the presence or absence of 1 µM of GW9662 and the results monitored by ³¹P and diffusion-weighted ¹H NMR spectroscopy. GW9662 completely reversed PB-induced NMR-visible lipid and total choline accumulation in ¹H spectra and glycerophosphocholine and β-NTP in ³¹P spectra. In addition, pre-incubation with GW9662 significantly reduced PB-induced caspase-3 activation, reversed the G1 block as measured by flow cytometry, and otherwise had little effect on cell survival as measured by MTT assay. These results suggest that the NMR visible lipid accumulation and apoptosis induced by PB treatment occurs through a mechanism that is mediated by PPAR-γ.