Momordica charantia lectin exhibits antitumor activity towards hepatocellular carcinoma.
Palabras clave
Abstracto
BACKGROUND
The incidence and mortality of hepatocellular carcinoma (HCC) remain high worldwide. Drug screening from natural plants is one of the potential therapeutic approaches on HCC.
METHODS
The antitumor effect of momordica charantia lectin (MCL) was examined, using MTT, colony formation, AnnexinV/PI staining, western blot and animal model.
RESULTS
MCL treatment induced G2/M phase arrest, autophagy, DNA fragmentation, mitochondrial injury, and subsequently cell apoptosis in HCC cells. Activation of caspase and MAPK pathway was involved in MCL-induced apoptosis. In vitro and in vivo studies showed that up-regulation of truncated Bid (tBid) upon MCL treatment. Correlation analysis revealed that Bid expression was reversely associated with the IC50 of MCL. Bid suppression using Bid siRNA, BI-6C9 (Bid inhibitor) and Z-IETD-FMK (caspase 8 inhibitor) dramatically attenuated MCL-induced cell proliferation inhibition, caspase 3 activation, ΔΨm depolarization and apoptosis. In addition, combination of MCL and sorafenib exerted stronger lethal activity towards HCC in vitro and in vivo.
CONCLUSIONS
Our data show that the natural compound MCL manifests antitumor activities towards HCC and therefore suggest MCL as a promising chemotherapeutic agent.
