Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.mrfmmm.2007.06.005
Title: Inhibition of telomerase activity and human telomerase reverse transcriptase gene expression by histone deacetylase inhibitor in human brain cancer cells
Authors: Khaw, A.K. 
Silasudjana, M.
Banerjee, B. 
Hande, M.P. 
Suzuki, M.
Baskar, R. 
Keywords: Cancer chemotherapy
Genome Instability
Glioblastoma and medulloblastoma
Histone deacetylase inhibitors
Telomeres and telomerase
Issue Date: 2007
Source: Khaw, A.K., Silasudjana, M., Banerjee, B., Hande, M.P., Suzuki, M., Baskar, R. (2007). Inhibition of telomerase activity and human telomerase reverse transcriptase gene expression by histone deacetylase inhibitor in human brain cancer cells. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 625 (1-2) : 134-144. ScholarBank@NUS Repository. https://doi.org/10.1016/j.mrfmmm.2007.06.005
Abstract: 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 0.5-3.0 μM TSA for 24 h. 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 2 μM 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. © 2007 Elsevier B.V. All rights reserved.
Source Title: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
URI: http://scholarbank.nus.edu.sg/handle/10635/25086
ISSN: 00275107
DOI: 10.1016/j.mrfmmm.2007.06.005
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