Momordica Charantia lectin exhibits antitumor activity towards hepatocellular carcinoma
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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.
KeywordsMCL Bid Apoptosis Hepatocellular carcinoma
Momordica Charantia lectin
acidic vesicular organelles
Mitogen activated protein kinase
We thank Dr. George Gong Chen from The Chinese University of Hong Kong for his valuable advices on our study. This work was supported by grants from the National Natural Science Foundation of China (No. 81201717) and the China Postdoctoral Science Foundation (No. 2012 M511867).
Conflicts of interest
There are no conflicts of interest.
- 16.Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, Double JA, Everitt J, Farningham DA, Glennie MJ, Kelland LR, Robinson V, Stratford IJ, Tozer GM, Watson S, Wedge SR, Eccles SA (2010) Guidelines for the welfare and use of animals in cancer research. Br J Cancer 102:1555–1577PubMedCentralPubMedCrossRefGoogle Scholar
- 19.Liu GY, Liao YF, Hsu PC, Chang WH, Hsieh MC, Lin CY, Hour TC, Kao MC, Tsay GJ, Hung HC (2006) Antizyme, a natural ornithine decarboxylase inhibitor, induces apoptosis of haematopoietic cells through mitochondrial membrane depolarization and caspases’ cascade. Apoptosis 11:1773–1788PubMedCrossRefGoogle Scholar
- 20.Kavitha K, Kowshik J, Kishore TK, Baba AB, Nagini S (2013) Astaxanthin inhibits NF-kappaB and Wnt/beta-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochim Biophys Acta 1830:4433–4444PubMedCrossRefGoogle Scholar
- 24.Dong Y, Xiong M, Duan L, Liu Z, Niu T, Luo Y, Wu X, Xu C, and Lu C (2014) H2AX phosphorylation regulated by p38 is involved in Bim expression and apoptosis in chronic myelogenous leukemia cells induced by imatinib. ApoptosisGoogle Scholar