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Inhibition of β‐oxidative respiration is a therapeutic window associated with the cancer chemo‐preventive activity of PPARγ agonists
Author(s) -
Andela Valentine B.,
Altuwaijri Saleh,
Wood James,
Rosier Randy N.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.082
Subject(s) - oxidative phosphorylation , trimetazidine , chemistry , peroxisome proliferator activated receptor , fatty acid synthase , troglitazone , beta oxidation , pharmacology , biochemistry , endocrinology , medicine , metabolism , lipid metabolism , biology , receptor
We demonstrate expression and coordinate induction of PPAR γ 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.