title: Momordica charantia lectin exhibits antitumor activity towards hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China, ls01zzy@hotmail.com.
authors.forename: Chris Zhiyi
authors.initials: CZ
authors.lastname: Zhang
authors.forename: Evandro Fei
authors.initials: EF
authors.lastname: Fang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zhang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008819:Mice, Nude; D029777:Momordica charantia; D037121:Plant Lectins / Q000494:pharmacology / Q000627:therapeutic use*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D037121:Plant Lectins; D053148:Caspase 3