title: Ethanol Mediates Cell Cycle Arrest and Apoptosis in SK-N-SH Neuroblastoma Cells.
abstract: BACKGROUND
  The mechanisms of cell or organ damage by chronic alcohol consumption are still poorly understood. The present study aimed to investigate the role of the mitogen-activated protein kinases during ethanol-induced damage to SK-N-SH neuroblastoma cells.
  
  
  METHODS
  Cells were treated with ethanol and subsequently analyzed for cell morphology, viability, and DNA fragmentation. Immunoblot analysis was performed to assess various proteins levels associated with cell cycle arrest and apoptosis after ethanol exposure.
  
  
  RESULTS
  Ethanol induced time- and dose-dependent cell death in SK-N-SH cells and increased c-Jun N-terminal protein kinase (JNK) activity in a time- and concentration dependent manner. In contrast, p38 kinase activity increased transiently. After treatment with JNK or p38 kinase inhibitors, ethanol-induced cell death significantly reduced. Ethanol-induced cell death was accompanied by increased cytochrome c release and caspase 3 activity observed at 12 h. In contrast, the level of anti-apoptotic Bcl-2 protein did not change. Ethanol also increased the phosphorylation of p53 and p53 activation was followed by an increase in the p21 tumor suppressor protein accompanied by a gradual decrease in phospho-Rb protein.
  
  
  CONCLUSIONS
  Our results suggest that ethanol mediates apoptosis of neuroblastoma cells by stimulating p53-related cell cycle arrest mediated through activation of the JNK-related pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Maria
authors.initials: M
authors.lastname: Lee
authors.affiliation: Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, USA.
authors.forename: Byoung-Joon
authors.initials: BJ
authors.lastname: Song
authors.affiliation: Department of Obstetrics and Gynecology, Kangdong Sacred Heart Hospital, Hallym University, Seoul, Korea.
authors.forename: Yongil
authors.initials: Y
authors.lastname: Kwon
keywords: Apoptosis; Ethanol; MAPK; Neuroblastoma cell line; p53