Reactive oxygen species-mitochondria pathway involved in FV-429-induced apoptosis in human hepatocellular carcinoma HepG2 cells.

Abstract

FV-429 is a newly synthesized flavonoid with a bis(2-hydroxyethyl) amino propoxy substitution. In this study, we investigate the anticancer effect of FV-429 both in vivo and in vitro. These data have shown that FV-429 could significantly inhibit tumor growth in mice inoculated with Heps hepatoma cells without evident toxicity. After the treatment of FV-429 (40 mg/kg), the inhibitory rate of tumor weight was 52.12%. Then, we performed diamidinophenylindole staining and annexin V/propidium iodide double-staining assay to investigate the apoptosis induced by FV-429 in HepG2 cells. Further research revealed that FV-429 induced apoptosis through the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl-2 ratios, collapse of mitochondrial membrane potential, the transposition of apoptotic-inducing factor and cytochrome c, caspase-3 and caspase-9 activation, and degradation of poly (ADP-ribose) polymerase. The accumulation of reactive oxygen species induced by FV-429 in HepG2 cells was also observed. Moreover, the mitogen-activated protein kinases, the downstream effect of reactive oxygen species accumulation including c-Jun N-terminal kinase and p38 mitogen-activated protein kinases, could be activated by FV-429. Taken together, our results provided a mechanistic framework for further exploration of FV-429 as a novel chemotherapy for human tumors.