Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10872910 | FEBS Letters | 2005 | 5 Pages |
Abstract
We demonstrate expression and coordinate induction of PPARγ and lipogenic enzymes (HMG-CoA synthase, HMG-CoA reductase and fatty acid synthase) in a murine lung alveolar carcinoma cell line (Line 1) treated with the PPARγ agonist troglitazone (TRO) [0-100 μM]. We postulate that TRO induces a shift in cellular energy metabolism towards fatty acid oxidation (β-oxidative respiration). Accordingly, co-treatment with TRO [30 μM] and increasing concentrations of trimetazidine (TMZ) [0.1-3 mM], an inhibitor of β-oxidation, results in a dose dependent decrease cellular ATP levels and a dose dependent induction of apoptosis. These findings, suggest that inhibition of β-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPARγ agonists.
Keywords
NADPH2TMZPDHTZDPPARγChemo-preventionHMG-CoAROSAdenosine TriphosphateATPFatty acidCellular energeticsTROTroglitazoneTrimetazidineThiazolidinedionethiazolidinedionesACLMethylenetetrahydrofolate reductasepyruvate dehydrogenaseredox controlGlucoseReactive oxygen speciesPeroxisome proliferator activated receptor gamma
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Authors
Valentine B. Andela, Saleh Altuwaijri, James Wood, Randy N. Rosier,