title: Influence of dichloroacetate (DCA) on lactate production and oxygen consumption in neuroblastoma cells: is DCA a suitable drug for neuroblastoma therapy?
abstract: Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO(2) and H(2)O (oxidative phosphorylation) even in the presence of oxygen (Warburg effect). Dichloroacetate (DCA) is a drug which is able to shift pyruvate metabolism from lactate to acetyl-CoA (tricarboxylic acid cycle) by indirect activation of pyruvate dehydrogenase (PDH). This can subsequently lead to an increased flow of oxygen in the respiratory chain, associated with enhanced generation of reactive oxygen species (ROS) which may cause apoptosis. In order to investigate if DCA may be suitable for neuroblastoma therapy, it was investigated on three human neuroblastoma cell lines whether DCA can reduce lactate production and enhance oxygen consumption. The data show, that DCA (in the low millimolar range) is able to reduce lactate production, but there was only a slight shift to increased oxygen consumption and almost no effect on cell vitality, proliferation and apoptosis of the three cell lines investigated. Therefore, DCA at low millimolar concentrations seems to be only of minor efficacy for neuroblastoma treatment.
authors.affiliation: Department of General Paediatrics and Oncology/Haematology, University of Tübingen, Tübingen, Germany.
authors.forename: Marena Rebekka
authors.initials: MR
authors.lastname: Niewisch
authors.forename: Zyrafete
authors.initials: Z
authors.lastname: Kuçi
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Mirjam
authors.initials: M
authors.lastname: Sautter
authors.forename: Lea
authors.initials: L
authors.lastname: Krampen
authors.forename: Beate
authors.initials: B
authors.lastname: Deubzer
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Gernot
authors.initials: G
authors.lastname: Bruchelt
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002952:Citric Acid Cycle; D003470:Culture Media / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis*; D008928:Mitochondria; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003470:Culture Media; D011768:Pyruvate Dehydrogenase Complex; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid; D010100:Oxygen