biostudies-otherBonnet S37-51https://www.ebi.ac.uk/biostudies/studies/S-ECPF-GEOD-6014EurocanPlatformThe unique metabolic profile of most cancers (aerobic glycolysis) might confer apoptosis-resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential and low expression of the K+ channel Kv1.5, both contributing to apoptosis-resistance. Dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases mitochondrial membrane potential, increases mitochondrial-H2O2 and activates Kv channels in all cancer, but not normal cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation and tumor growth in vitro and in vivo, without apparent toxicity. Molecular inhibition of PDK2 by siRbiostudies-othertranscription profiling by arrayEurocanPlatformUnknown11Cancer cellHomo sapiensLopaschuk GDHarry GLee CTHaromy AThebaud BAllalunis-Turner JPuttagunta LThompson RAndrade MAPorter CJMichelakis EDBonnet SBeaulieu CArcher SLHashimoto KfalseTranscription profiling of lung carcinoma and brain glioblastoma cells were analalyzed, with microarrays run both for control and treatment with dichloroacetate reveals a mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis inhibits cancer growthThe unique metabolic profile of most cancers (aerobic glycolysis) might confer apoptosis-resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential and low expression of the K+ channel Kv1.5, both contributing to apoptosis-resistance. Dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases mitochondrial membrane potential, increases mitochondrial-H2O2 and activates Kv channels in all cancer, but not normal cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation and tumor growth in vitro and in vivo, without apparent toxicity. Molecular inhibition of PDK2 by siR2016-04-14T14:38:51Z2007 Jan2016-04-14T14:38:51Z2016-04-14T14:38:51ZS-ECPF-GEOD-6014GSE6014E-GEOD-6014EFO_0000322EFO_0000519EFO_0001071E-GEOD-6014