Jardim-Messeder 2016 Anticancer Res
| Jardim-Messeder D, Moreira-Pacheco F (2016) 3-Bromopyruvic acid inhibits Tricarboxylic acid cycle and glutaminolysis in HepG2 cells. Anticancer Res 36:2233-41. |
Jardim-Messeder D, Moreira-Pacheco F (2016) Anticancer Res
Abstract: 3-bromopyruvate (3BrPA) is an antitumor agent able to inhibit aerobic glycolysis and oxidative phosphorylation, therefore inducing cell death. However, cancer cells are also highly dependent of glutaminolysis and tricarboxylic acid cycle (TCA) regarding survival and 3BrPA action in these metabolic routes is poorly understood.
The effect of 3BrPA was characterized in mice liver and kidney mitochondria, as well as in human HepG2 cells.
Low concentration of 3-BrPA significantly affected both glutaminolysis and TCA cycle functions, through inhibition of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and succinate dehydrogenase. Additionally, 3-BrPA treatment significantly decreased the reduced status of thiol groups in HepG2 cells without proportional increase of oxidizing groups, suggesting that these chemical groups are the target of alkylation reactions induced by 3-BrPA.
This work demonstrates, for the first time, the effect of 3-BrPA in glutaminolysis and TCA cycle. Our results suggest that the combined action of 3-BrPA in glutaminolysis, TCA and glycolysis, inhibiting steps downstream of the glucose and glutamine metabolism, has an antitumor effect.
Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. • Keywords: 3-Bromopyruvate, HepG2 cells, TCA cycle, Glutaminolysis, Liver mitochondria • Bioblast editor: Kandolf G • O2k-Network Lab: BR Rio de Janeiro Galina A
Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology
Pathology: Cancer
Organism: Mouse Tissue;cell: Liver, Kidney Preparation: Isolated mitochondria
Coupling state: OXPHOS, ET
Pathway: CIV, NS
HRR: Oxygraph-2k
Labels, 2017-05
