PF-04691502 triggers cell cycle arrest, apoptosis and inhibits the angiogenesis in hepatocellular carcinoma cells.
Toxicol Lett
; 220(2): 150-6, 2013 Jul 04.
Article
em En
| MEDLINE
| ID: mdl-23639247
ABSTRACT
Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in the world. The aim of the present study is to determine the antitumor effect of PF-04691502, a potent inhibitor of PI3K and mTOR kinases, on the apoptosis and angiogenesis of the hepatoma cancer cells. Our results indicate that treatment of cancer cells with PF-04691502 reduces cell viability and inhibits cell growth in a dose-dependent manner. PF-04691502 triggers apoptosis via a mitochondrial pathway, accompanied by activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). Pre-treatment of hepatoma cells with the caspase-3 inhibitor (z-DEVD-fmk) blocks the PF-04691502-induced death of these cells. In addition, growth factors-induced tube formation and the migration of HUVECs are markedly inhibited by PF-04691502 treatment. The mechanisms of anti-angiogenesis of PF-04691502 are associated with inhibiting the expression of VEGF and HIF-1α. Based on the overall results, we suggest that PF-04691502 reduces hepatocellular carcinoma cell viability, induces cell apoptosis, and inhibits cell growth and tumor angiogenesis, implicating its potential therapeutic value in the treatment of HCC.
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Base de dados:
MEDLINE
Assunto principal:
Piridonas
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Pirimidinas
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Apoptose
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Carcinoma Hepatocelular
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Pontos de Checagem da Fase G1 do Ciclo Celular
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Neoplasias Hepáticas
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article