Lovastatin enhances phenylbutyrate-induced MR-visible glycerophosphocholine but not apoptosis in DU145 prostate cells.
In this study the effects of lovastatin on DU145 prostate cancer cells treated with phenylbutyrate (PB) was investigated in order to determine the NMR-detectable metabolic changes resulting from the cooperative activity of these two agents. DU145 cells were perfused with PB in the presence or absence of 10 microM of the HMG-CoA reductase inhibitor lovastatin, and the results monitored by 31P and diffusion-weighted 1H NMR spectroscopy. Lovastatin had additive effects on the PB-induced NMR-visible total choline in 1H spectra, and glycerophosphocholine in 31P spectra but no significant effect on NMR-visible lipid. Moreover, lovastatin had no effect on the ability of PB to either promote the formation of oil red O-detectable lipid droplets or arrest the cell cycle. The most remarkable observations from these studies were that lovastatin enhanced the increase in glycerophosphocholine while reversing late markers of apoptosis and the loss of NTP caused by PB. These results identify a branch point separating the neutral lipid production and the apoptotic cell death caused by the actions of differentiating agents.
Milkevitch
Matthew
M
Molecular Imaging Laboratory, Department of Radiology, University of Pennsylvania School of Medicine, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA.
Jeitner
Thomas M
TM
Beardsley
Nancy J
NJ
Delikatny
E James
EJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005994:Glycerophosphates / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008148:Lovastatin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D010654:Phenylbutyrates / Q000378:metabolism / Q000494:pharmacology; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism*; D011471:Prostatic Neoplasms; D011859:Radiography
D005994:Glycerophosphates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010654:Phenylbutyrates; D010767:Phosphorylcholine; D008148:Lovastatin; D053148:Caspase 3