PF-04691502 triggers cell cycle arrest, apoptosis and inhibits the angiogenesis in hepatocellular carcinoma cells

• PF-04691502 induces cell cycle arrest through regulating cyclinD1 and p27.
• PF-04691502 triggers apoptosis via a mitochondrial pathway.
• Growth factors-induced tube formation and migration of HUVECs are inhibited by PF-04691502 treatment.
• PF-04691502 inhibits the expression of VEGF and HIF-1α.

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.