OBJECTIVE: To investigate the apoptotic effects and underlying molecular mechanisms of Celastrus orbiculatus (C. orbiculatus) extract in human hepa- tocellular carcinoma cells. METHODS: Human hepatocellular carcin...OBJECTIVE: To investigate the apoptotic effects and underlying molecular mechanisms of Celastrus orbiculatus (C. orbiculatus) extract in human hepa- tocellular carcinoma cells. METHODS: Human hepatocellular carcinoma cells (HCCLM6) were treated with C. orbiculatus extract (COE) at different nontoxic concentrations (10, 20, 40, 80, and 160 IJg/mL). The effect of COE on HC-CLM6 viability was examined using 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Cellular apoptosis following COE treatment was assessed by flow cytometry and western blot analysis. RESULTS: COE significantly inhibited cell viability and induced apoptosis of HCCLM6 cells in a dose-dependent manner. Apoptosis was accompa- nied by increased Bax expression and decreased Bcl-2 expression. In addition, COE treatment led to the release of cytochrome c, activation of cas- pase-3, and cleavage of poly (ADP-ribose) poly- merase (PARP). Furthermore, activation of extracel- lular signal-regulated kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK) phosphorylation, and down-regulation of Akt phosphorylation was ob- served. CONCLUSION: COE induces mitochondrial-mediat- ed, caspase-dependent apoptosis in HCCLM6 cells, which might be attributed to the activation of mito- gen-activated protein kinase (MAPK) and inhibition of Akt signaling pathways. These data suggest that COE may be a potential treatment for human hepa- tocellular carcinoma.展开更多
基金Supported by the National Natural Science Foundation of China(No.81173603 and No.81274141)State Administration of Traditional Chinese Medicine of China(No.0405ZP35)+3 种基金Jiangsu Provincial Social Development Project(No. BE2011738)the Natural Science Foundation of Jiangsu Province(No.BK2012686)Administration of Traditional Chinese Medicine of Jiangsu Province(No.LZ11210)and the Project of Cooperation between Yangzhou University and Yangzhou City(No.YZ2010157)
文摘OBJECTIVE: To investigate the apoptotic effects and underlying molecular mechanisms of Celastrus orbiculatus (C. orbiculatus) extract in human hepa- tocellular carcinoma cells. METHODS: Human hepatocellular carcinoma cells (HCCLM6) were treated with C. orbiculatus extract (COE) at different nontoxic concentrations (10, 20, 40, 80, and 160 IJg/mL). The effect of COE on HC-CLM6 viability was examined using 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Cellular apoptosis following COE treatment was assessed by flow cytometry and western blot analysis. RESULTS: COE significantly inhibited cell viability and induced apoptosis of HCCLM6 cells in a dose-dependent manner. Apoptosis was accompa- nied by increased Bax expression and decreased Bcl-2 expression. In addition, COE treatment led to the release of cytochrome c, activation of cas- pase-3, and cleavage of poly (ADP-ribose) poly- merase (PARP). Furthermore, activation of extracel- lular signal-regulated kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK) phosphorylation, and down-regulation of Akt phosphorylation was ob- served. CONCLUSION: COE induces mitochondrial-mediat- ed, caspase-dependent apoptosis in HCCLM6 cells, which might be attributed to the activation of mito- gen-activated protein kinase (MAPK) and inhibition of Akt signaling pathways. These data suggest that COE may be a potential treatment for human hepa- tocellular carcinoma.