Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1.
J Biol Chem
; 298(12): 102678, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36356901
ABSTRACT
Metformin, an antidiabetic drug, shows some potent antitumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here, we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor nuclear factor E2-related factor 2. In addition, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the nuclear factor E2-related factor 2-HMGCS1 axis, which might be a potential target in cancer prevention and treatment.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metformina
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2022
Tipo de documento:
Article