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.