Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment.
Transl Oncol
; 13(11): 100842, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-32781368
Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials. Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines. Our results showed that 6-AN has sensitizing properties to metformin cytotoxicity. The combination of metformin and 6-AN decreased glucose consumption and lactate production, altered the mitochondrial potential and redox balance, and thereby blocked melanoma cell progression, directing cells to apoptosis and necrosis. To our knowledge, this is the first study describing the effect of this combination. Future preclinical studies should be performed to reveal the biological relevance of this finding.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Transl Oncol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
Estados Unidos