title: Celastrus orbiculatus extract induces mitochondrial-mediated apoptosis in human hepatocellular carcinoma cells.
abstract: 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 microg/mL). The effect of COE on HCCLM6 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nursing, School of Medicine, Yangzhou University, Yangzhou 225001, China.
authors: Hua
authors: H
authors: Zhang
authors: Yayun
authors: Y
authors: Qian
authors: Yanqing
authors: Y
authors: Liu
authors: Guoqing
authors: G
authors: Li
authors: Pingfang
authors: P
authors: Cui
authors: Yaodong
authors: Y
authors: Zhu
authors: Hui
authors: H
authors: Ma
authors: Xue
authors: X
authors: Ji
authors: Shiyu
authors: S
authors: Guo
authors: Hisamits
authors: H
authors: Tadashi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D031247:Celastrus / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3