RT Journal Article
SR Electronic
T1 3-Bromopyruvic Acid Inhibits Tricarboxylic Acid Cycle and Glutaminolysis in HepG2 Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2233
OP 2241
VO 36
IS 5
A1 DOUGLAS JARDIM-MESSEDER
A1 FABIANA MOREIRA-PACHECO
YR 2016
UL http://ar.iiarjournals.org/content/36/5/2233.abstract
AB Background/Aim: 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. Materials and Methods: The effect of 3BrPA was characterized in mice liver and kidney mitochondria, as well as in human HepG2 cells. Results: 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. Conclusion: 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.