| 1 | Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells显示文摘AIM: To investigate the anti-cancer mechanisms of Korean mistletoe lectin (Viscum album coloratum agglutinin,VCA) using a human colon cancer cell line (COLO). METHODS: Cytotoxic effects of VCA on COLO cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved,the expression of various pro-caspases,anti-apoptotic proteins,and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells,cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors. RESULTS: VCA killed COLO cells in a time-and dose-dependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2,-3,-8,and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein,nuclear factor-κB,X-linked inhibitor of apoptosis protein,and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1,among the death receptors examined,was involved in apoptosis of COLO cells,evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases,particularly caspase-8,by tumor necrosis factor receptor 1 antagonizing antibody.CONCLUSION: VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of anti-apoptotic proteins,in part through the tumor necrosis factor receptor 1 signaling pathway. | Lee-Yong Khil Wi Kim Suyun Lyu Won Bong Park Ji-Won Yoon Hee-Sook Jun | 2007 | World Journal of Gastroenterology2007，13，20： | 4 |
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