| Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine. | |
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MedLine Citation:
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PMID: 19653337 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To investigate the potential effects of chelidonine, the main alkaloid of Chelidonium majus, on telomerase activity and its regulation in HepG2 cells. METHODS: Cytotoxicity of chelidonine for HepG2 cells was determined by neutral red assay. A modified polymerase chain reaction (PCR)-based telomerase repeat amplification protocol was used to estimate relative telomerase activity in chelidonine-treated cells in comparison with the untreated control cells. Relative expression level of the catalytic subunit of telomerase (hTERT) gene and P-glycoprotein (pgp) were estimated using semi-quantitative real-time reverse transcription-PCR (RT-PCR). Cell senescence in treated cells was demonstrated using a beta-galactosidase test. RESULTS: Cytotoxicity of chelidonine in HepG2 cells was not dose-dependent and tended to reach plateau immediately after the living cells were reduced in number to slightly higher than 50%. However, 12 micromol/L concentration of chelidonine was considered as LD(50), where the maximal attainable effects were realized. Real-time RT-PCR data showed that the expression of pgp increased three-fold in chelidonine treated HepG2 cells in comparison with the untreated controls. Morphologically, treated HepG2 cells showed apoptotic features after 24 h and a small fraction of cells appeared with single blister cell death. The relative expression level of Bcl-2 dropped to less than 50% of control cells at a sub-apoptotic concentration of chelidonine and subsequently increased to higher than 120% at LD(50). Telomerase activity was reduced considerably after administration of very low doses of chelidonine, whereas higher concentrations of chelidonine did not remarkably enhance the effect. Real-time RT-PCR experiments indicated a drastic decrease in expression level of hTERT subunit of telomerase under treatment with chelidonine. Repeated treatment of cells with very low doses of chelidonine caused a decline in growth rate by 4 wk and many of the cells appeared to be aged with large volume and dark staining in the beta-galactosidase assay. CONCLUSION: Chelidonine reduces telomerase activity through down-regulation of hTERT expression. Senescence induction might not be directly caused by reducing telomerase activity as it occurs after a few population doublings. |
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Authors:
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Sakineh Kazemi Noureini; Michael Wink |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: World journal of gastroenterology : WJG Volume: 15 ISSN: 1007-9327 ISO Abbreviation: World J. Gastroenterol. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-04 Completed Date: 2009-12-01 Revised Date: - |
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: 3603-10 Citation Subset: IM |
Affiliation:
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Department of Biology, Faculty of Basic Sciences, Tarbiat Moallem University of Sabzevar, Sabzevar, Iran. s-kazemi@sttu.ac.ir |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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analysis Apoptosis / drug effects Benzophenanthridines / pharmacology* Cell Aging / drug effects Cell Line, Tumor Chelidonium / chemistry Down-Regulation / drug effects Genes, bcl-2 / drug effects Humans P-Glycoprotein / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Telomerase / metabolism* beta-Galactosidase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Benzophenanthridines; 0/P-Glycoprotein; 0/Proto-Oncogene Proteins c-bcl-2; 476-32-4/chelidonine; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 3.2.1.23/beta-Galactosidase |
| Comments/Corrections | |
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