articleJournal of Clinical InvestigationDec 28, 2009BRONZE OA

Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction

The University of Texas Health Science Center at Houston · The University of Texas MD Anderson Cancer Center

PubMed
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Abstract

The traditional view is that cancer cells predominately produce ATP by glycolysis, rather than by oxidation of energy-providing substrates. Mitochondrial uncoupling--the continuing reduction of oxygen without ATP synthesis--has recently been shown in leukemia cells to circumvent the ability of oxygen to inhibit glycolysis, and may promote the metabolic preference for glycolysis by shifting from pyruvate oxidation to fatty acid oxidation (FAO). Here we have demonstrated that pharmacologic inhibition of FAO with etomoxir or ranolazine inhibited proliferation and sensitized human leukemia cells--cultured alone or on bone marrow stromal cells--to apoptosis induction by ABT-737, a molecule that releases…

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