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Momordica charantia lectin exhibits antitumor activity towards hepatocellular carcinoma
Chris Zhiyi Zhang1, Evandro Fei Fang, Hai-Tao Zhang
1Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China, ls01zzy@hotmail.com.
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.
Conclusion:
Our data show that the natural compound MCL manifests antitumor activities towards HCC and therefore suggest MCL as a promising chemotherapeutic agent.
