3-Bromopyruvic Acid Inhibits Tricarboxylic Acid Cycle and Glutaminolysis in HepG2 Cells.
Anticancer Res
; 36(5): 2233-41, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-27127128
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piruvatos
/
Ciclo do Ácido Cítrico
/
Glutamina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Grécia