| Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells. | |
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MedLine Citation:
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PMID: 17373752 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: 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. CONCLUSION: 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. |
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Authors:
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Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: World journal of gastroenterology : WJG Volume: 13 ISSN: 1007-9327 ISO Abbreviation: World J. Gastroenterol. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-03-21 Completed Date: 2007-06-06 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100883448 Medline TA: World J Gastroenterol Country: China |
Other Details:
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Languages: eng Pagination: 1129-34 Citation Subset: IM |
Affiliation:
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Research Center for Eco-Environmental Sciences, The Chinese Academy of Sciences, Haidian District, Beijing 100085, China. wangjing@rcees.ac.cn |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Carcinoma, Hepatocellular
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metabolism*,
pathology Cell Cycle / drug effects*, physiology Cell Line, Tumor Cell Proliferation / drug effects Cyclin D1 / genetics, metabolism Cyclin-Dependent Kinase Inhibitor p21 / genetics, metabolism Cyclin-Dependent Kinases / genetics, metabolism Enzyme Inhibitors / pharmacology* Extracellular Signal-Regulated MAP Kinases / physiology Gene Expression Regulation / drug effects Humans Liver Neoplasms / metabolism*, pathology PPAR gamma / physiology Signal Transduction / physiology Sphingosine / analogs & derivatives*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 0/Enzyme Inhibitors; 0/N-acetylsphingosine; 0/PPAR gamma; 123-78-4/Sphingosine; 136601-57-5/Cyclin D1; EC 2.7.1.37/cyclin-dependent kinase-activating kinase; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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