title: Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells.
abstract: OBJECTIVE
  To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored.
  
  
  METHODS
  [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.
  
  
  RESULTS
  C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARgamma was upregulated. Addition of GW9662, which is a PPARgamma specific antagonist, could reserve the modulation action on CDK7.
  
  
  CONCLUSIONS
  Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARgamma activation. The ERK signaling pathway was involved in this process.
authors: Research Center for Eco-Environmental Sciences, The Chinese Academy of Sciences, Haidian District, Beijing 100085, China. wangjing@rcees.ac.cn
authors: Jing
authors: J
authors: Wang
authors: Xiao-Wen
authors: XW
authors: Lv
authors: Jie-Ping
authors: JP
authors: Shi
authors: Xiao-Song
authors: XS
authors: Hu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; C064769:N-acetylsphingosine; D047495:PPAR gamma; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D013110:Sphingosine; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human