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Phenylbutyrate induces apoptosis and lipid accumulations via a peroxisome proliferator‐activated receptor gamma‐dependent pathway
Author(s) -
Milkevitch Matthew,
Beardsley Nancy J.,
Delikatny E. James
Publication year - 2010
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1484
Subject(s) - du145 , apoptosis , chemistry , peroxisome proliferator activated receptor , proton nmr , flow cytometry , receptor , nuclear magnetic resonance spectroscopy , biophysics , biochemistry , microbiology and biotechnology , biology , cancer cell , stereochemistry , medicine , cancer , lncap
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 31 P and diffusion‐weighted 1 H NMR spectroscopy. GW9662 completely reversed PB‐induced NMR‐visible lipid and total choline accumulation in 1 H spectra and glycerophosphocholine and β ‐NTP in 31 P spectra. In addition, pre‐incubation with GW9662 significantly reduced PB‐induced caspase‐3 activation, reversed the G 1 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 . Copyright © 2010 John Wiley & Sons, Ltd.