| Inhibition of telomerase activity and human telomerase reverse transcriptase gene expression by histone deacetylase inhibitor in human brain cancer cells. | |
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MedLine Citation:
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PMID: 17669439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of the present study is to investigate the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the cell growth, apoptosis, genomic DNA damage and the expression of telomerase and associated factors in human normal and brain cancer cells. Here, human normal un-transformed fibroblasts (MRC-5), human normal hTERT-immortalised fibroblasts (hTERT-BJ1) and human brain cancer cell lines (glioblastoma cell line, A-172 and medulloblastoma cell line, ONS-76) were treated with 0.5-3.0microM TSA for 24h. Exposure to TSA resulted in apoptosis in a dose-dependent manner in the brain cancer cells. Glioblastoma cell line (A-172) displayed higher sensitivity to TSA-induced cell killing effect and apoptosis than the medulloblastoma cell line (ONS-76). The brain cancer cell lines and hTERT-BJ1 cell line displayed significant inhibition in telomerase activity and hTERT mRNA level after 2microM TSA treatment. Elevated expressions of p53 and p21 with a decrease in cyclin-D level supported the observation on cell cycle arrest following TSA treatment. Upregulation of Bax and cytochrome c correlated with the apoptotic events in TSA-treated cells. This study suggests that telomerase and hTERT might be the primary targets of TSA which may have the potential to be used as a telomerase inhibitor in cancer therapy. |
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Authors:
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Aik Kia Khaw; Miranti Silasudjana; Birendranath Banerjee; Masao Suzuki; Rajamanickam Baskar; M Prakash Hande |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-26 |
Journal Detail:
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Title: Mutation research Volume: 625 ISSN: 0027-5107 ISO Abbreviation: Mutat. Res. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-11-05 Completed Date: 2007-12-13 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0400763 Medline TA: Mutat Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 134-44 Citation Subset: IM |
Affiliation:
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Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Brain Neoplasms / drug therapy*, enzymology, genetics, pathology Cell Cycle / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects DNA Repair DNA Replication / drug effects Gene Expression / drug effects Genomic Instability / drug effects, physiology Histone Deacetylase Inhibitors* Humans Hydroxamic Acids / pharmacology In Situ Hybridization, Fluorescence RNA, Messenger / genetics, metabolism RNA, Neoplasm / genetics, metabolism Telomerase / antagonists & inhibitors*, genetics |
| Chemical | |
Reg. No./Substance:
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0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/RNA, Messenger; 0/RNA, Neoplasm; 58880-19-6/trichostatin A; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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