Influence of Dichloroacetate (DCA) on Lactate Production and Oxygen Consumption in Neuroblastoma Cells: Is DCA a Suitable Drug for Neuroblastoma Therapy?

Cellular Physiology and Biochemistry

关键词: Dichloroacetate;    Lactate;    Neuroblastoma;    Oxygen consumption;    Warburg effect;   

DOI  :  10.1159/000338492

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO₂ and H₂O (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.

【 授权许可】

CC BY-NC-ND