title: Ursodeoxycholic acid induces apoptosis of hepatocellular carcinoma cells in vitro.
abstract: OBJECTIVE
  Ursodeoxycholic acid (UDCA) is widely used to treat chronic liver diseases, and its cytoprotective effect on normal hepatocytes has been shown. This study aimed to investigate the apoptotic effects of UDCA on hepatocellular carcinoma (HCC) cells and the underlying molecular events in vitro.
  
  
  METHODS
  HCC cells were treated by UDCA at different doses and periods of time to assess cell morphology, viability, apoptosis and gene expression using methyl thiazolyl tetrazolium (MTT), Annexin V/propidium iodide (PI) stain, transferase dUTP nick end labeling (TUNEL), enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and quantitative reverse transcription polymerase chain reaction, respectively.
  
  
  RESULTS
  UDCA treatment reduced cell viability but induced HCC cell apoptosis in dose-dependent and time-dependent manners. UDCA arrested HepG2 cells at phase S of the cell cycle. At the gene levels, UDCA downregulated Bcl-2 and second mitochondria-derived activator of caspase (Smac) protein expressions, but upregulated Bax and Livin proteins in HCC cells. At the highest concentration, UDCA inhibited Livin mRNA expression but increased Smac and caspase-3 mRNA expressions as well as the activity of caspase-3 in HCC cells.
  
  
  CONCLUSIONS
  The induction of HCC cell apoptosis by UDCA was dose-dependent and time-dependent and was mediated by the regulation of Bax to Bcl-2 ratio, the expressions of Smac and Livin, and caspase-3 expression and activity.
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Lu Juan
authors.initials: LJ
authors.lastname: Shan
authors.forename: Yue Jian
authors.initials: YJ
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Xiao Guang
authors.initials: XG
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000187:drug effects / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000235:genetics; D008113:Liver Neoplasms / Q000188:drug therapy*; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000235:genetics; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C419866:BIRC7 protein, human; D002756:Cholagogues and Choleretics; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D051028:bcl-2-Associated X Protein; D014580:Ursodeoxycholic Acid; D053148:Caspase 3
keywords: apoptosis; gene expression; hepatocellular carcinoma; ursodeoxycholic acid