LC/MS/MS method revealed that lung cancer cells exhibited distinct metabolite profiles upon the treatment with different pyruvate dehydrogenase kinases (PDKs) inhibitors

Pyruvate dehydrogenase kinases (PDKs) dominates the critical switch between mitochondria-based respiration and cytoplasm-based glycolysis by controlling pyruvate dehydrogenase (PDH) activity. Upregulated PDKs plays a great role in the Warburg effect in cancer cells and accordingly presents a therapeutic target. Dichloroacetate (DCA) and AZD7545 are the two most well-known PDKs inhibitors exhibiting distinct pharmacological profiles. DCA showed anticancer effects in various preclinical models and clinical studies, while the primary preclinical indication of AZD7545 was on the improvement of glucose control in type 2 diabetes. Little, if any, study has been undertaken to elucidate the effects of PDKs inhibition on the metabolites in the tricarboxylic acid (TCA) cycle. Herein the metabolite alterations of lung cancer cells (A549) upon the treatment with PDKs inhibitors were studied using a reliable liquid chromatography-based tandem mass spectrometry (LC-MS/MS) method. The developed method was validated for ...