title: Momordica Charantia lectin, a type II ribosome inactivating protein, exhibits antitumor activity toward human nasopharyngeal carcinoma cells in vitro and in vivo.
abstract: The incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions, including southern China, northern Africa, and North America. One of the promising therapeutic approaches on NPC is drug screening from natural products, such as components from traditional Chinese medicine. In this study, the antitumor activity of Momordica charantia lectin (MCL), a type II ribosome inactivating protein from bitter gourd, on NPC was investigated. MCL evinced potent cytotoxicity toward NPC CNE-1 (IC(50) = 6.9) and CNE-2 (IC(50) = 7.4) cells but minimally affected normal NP 69 cells. Further investigation disclosed that MCL induced apoptosis, DNA fragmentation, G(1)-phase arrest, and mitochondrial injury in both types of NPC cells. The reduction of cyclin D1 and phosphoretinoblastoma (Rb) protein expression contributed to arrest at G(1)-phase of the cell cycle. These events were associated with regulation of mitogen-activated protein kinases (MAPK; including p38 MAPK, JNK, and ERK) phosphorylation and promoted downstream nitric oxide (NO) production. Concurrent administration of the p38 MAPK inhibitor SB-203580 significantly diminished NO production and lethality of MCL toward NPC cells. Further studies revealed that MCL increased cytochrome c release into the cytosol, activated caspases-8, -9, and -3, and enhanced production of cleaved PARP, subsequently leading to DNA fragmentation and apoptosis. Finally, an intraperitoneal injection of MCL (1.0 mg/kg/d) led to an average of 45% remission of NPC xenograft tumors subcutaneously inoculated in nude mice. This is the first article that unveils the potential of a type II RIP, MCL, for prevention and therapy of NPC.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Choh Ming Li Basic Medical Sciences Building, The Chinese University of Hong Kong, Hong Kong, People's Republic of China. b021770@mailserv.cuhk.edu.hk.
authors.forename: Evandro Fei
authors.initials: EF
authors.lastname: Fang
authors.forename: Chris Zhi Yi
authors.initials: CZ
authors.lastname: Zhang
authors.forename: Tzi Bun
authors.initials: TB
authors.lastname: Ng
authors.forename: Jack Ho
authors.initials: JH
authors.lastname: Wong
authors.forename: Wen Liang
authors.initials: WL
authors.lastname: Pan
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Ye
authors.forename: Yau Sang
authors.initials: YS
authors.lastname: Chan
authors.forename: Wing Ping
authors.initials: WP
authors.lastname: Fong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D037102:Lectins / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D008564:Membrane Potentials; D051379:Mice; D008819:Mice, Nude; D029777:Momordica charantia / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D010936:Plant Extracts / Q000378:metabolism* / Q000494:pharmacology*; D012074:Remission Induction; D054788:Ribosome Inactivating Proteins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D037102:Lectins; D010936:Plant Extracts; D054788:Ribosome Inactivating Proteins