Celastrus orbiculatus extract induces mitochondrial-mediated apoptosis in human hepatocellular carcinoma cells  

作　　者：Hua Zhang Yayun Qian Yanqing Liu Guoqing Li Pingfang Cui Yaodong Zhu Hui Ma Xue Ji Shiyu Guo Hisamits Tadashi 

机构地区：[1]Department of Nursing,School of Medicine,Yangzhou University [2]Institute of Traditional Chinese Medicine and Western Medicine,School of Medicine,Yangzhou University [3]Traditional Chinese Medicine Division,Clinical Medical School,Yangzhou University [4]Department of Physiology,School of Medicine,Showa University,1-5-8 Hatanodai,Tokyo 142-8555,Japan

出　　处：《Journal of Traditional Chinese Medicine》2012年第4期621-626,共6页中医杂志（英文版）

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);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)

摘　　要：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.OBJECTIVE:To investigate the apoptotic effects and underlying molecular mechanisms of Celastrus orbiculatus(C.orbiculatus) extract in human hepatocellular 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 μg/mL).The effect of COE on HC-CLM6 viability was examined using 3-(4,5-dimethylthiazol-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 accompanied by increased Bax expression and decreased Bcl-2 expression.In addition,COE treatment led to the release of cytochrome c,activation of caspase-3,and cleavage of poly(ADP-ribose) polymerase(PARP).Furthermore,activation of extracellular signal-regulated kinase(ERK),p38 kinase,and c-Jun N-terminal kinase(JNK) phosphorylation,and down-regulation of Akt phosphorylation was observed.CONCLUSION:COE induces mitochondrial-mediated,caspase-dependent apoptosis in HCCLM6 cells,which might be attributed to the activation of mitogen-activated protein kinase(MAPK) and inhibition of Akt signaling pathways.These data suggest that COE may be a potential treatment for human hepatocellular carcinoma.

关 键 词：Celastrus Apoptosis Carcinoma  hepa-tocellular MITOCHONDRIA CASPASES Mitogen-activat-ed protein kinase 

分 类 号：R285[医药卫生—中药学] R735.7[医药卫生—中医学]