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Liquid Chromatography-Tandem Mass Spectrometry Method Revealed that Lung Cancer Cells Exhibited Distinct Metabolite Profiles upon the Treatment with Different Pyruvate Dehydrogenase Kinase Inhibitors
Zhang, Wen; Hu, Xiaohui; Zhou, Wei; Tam, Kin Yip
2018-09
Source PublicationJOURNAL OF PROTEOME RESEARCH
ISSN1535-3893
Volume17Issue:9Pages:3012-3021
AbstractPyruvate dehydrogenase kinases (PDKs) dominate the critical switch between mitochondria-based respiration and cytoplasm based glycolysis by controlling pyruvate dehydrogenase (PDH) activity. Up-regulated PDKs play a great role in the Warburg effect in cancer cells and accordingly present a therapeutic target. Dichloroacetate (DCA) and AZD7S4S are the two most-well-known PDK 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 II diabetes. Little, if any, study has been undertaken the elucidation of the effects of PDK inhibition on the metabolites in the tricarboxylic acid (TCA) cycle. Herein, the metabolite alterations of lung cancer cells (A549) upon the treatment with PDK inhibitors were studied using a reliable liquid-chromatography-based tandem mass spectrometry method. The developed method was validated for quantification of all common glycolysis and TCA cycle catabolites with good sensitivity and reproducibility, including glucose, pyruvate, lactate, acetyl coenzyme A, citrate, alpha-ketoglutarate, fumarate, succinate, malate, and oxaloacetate. Our results suggested that A549 cells exhibited distinct metabolite profiles following the treatment with DCA or AZD7S4S, which may reflect the different pharmacological indications of these two drugs.
Keywordaerobic glycolysis AZD7545 dichloroacetate LC-MS/MS pyruvate dehydrogenase kinases cancer metabolism
DOI10.1021/acs.jproteome.8b00184
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS IDWOS:000444364700009
PublisherAMER CHEMICAL SOC
The Source to ArticleWOS
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Zhang, Wen,Hu, Xiaohui,Zhou, Wei,et al. Liquid Chromatography-Tandem Mass Spectrometry Method Revealed that Lung Cancer Cells Exhibited Distinct Metabolite Profiles upon the Treatment with Different Pyruvate Dehydrogenase Kinase Inhibitors[J]. JOURNAL OF PROTEOME RESEARCH,2018,17(9):3012-3021.
APA Zhang, Wen,Hu, Xiaohui,Zhou, Wei,&Tam, Kin Yip.(2018).Liquid Chromatography-Tandem Mass Spectrometry Method Revealed that Lung Cancer Cells Exhibited Distinct Metabolite Profiles upon the Treatment with Different Pyruvate Dehydrogenase Kinase Inhibitors.JOURNAL OF PROTEOME RESEARCH,17(9),3012-3021.
MLA Zhang, Wen,et al."Liquid Chromatography-Tandem Mass Spectrometry Method Revealed that Lung Cancer Cells Exhibited Distinct Metabolite Profiles upon the Treatment with Different Pyruvate Dehydrogenase Kinase Inhibitors".JOURNAL OF PROTEOME RESEARCH 17.9(2018):3012-3021.
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