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Mol Med Rep ; 13(2): 1281-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26675978

RESUMO

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it has severe cardiotoxic side effects. The aim of the present study was to investigate the effects of resveratrol on the adenosine monophosphate-activated protein kinase (AMPK)/P53 pathway in mediating DOX-induced cytotoxicity. H9c2 cells were exposed to 5 µM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. DOX administration amplified P53 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression and decreased Bcl-2 expression in H9c2 cells. Resveratrol increased the cell viability and decreased the apoptotic rate. In addition, resveratrol markedly increased the phosphorylation of AMPK. Of note, resveratrol protected against DOX-induced increases of P53 and Bax and also prevented the downregulation of Bcl-2 in H9c2 cells. Furthermore, AMPK inhibitor Compound C abolished the protective effects of resveratrol. The results of the present study therefore indicated that resveratrol protected H9c2 cells from DOX-induced apoptosis via the AMPK/P53 pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular , Doxorrubicina/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Estilbenos/administração & dosagem , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética
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