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 to 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.
 This study is supported by Academic Research Fund, Ministry of Education and NUS. International Union Against Cancer (UICC, Switzerland) is acknoweldged for Yamagiwa-Yoshida Memorial International Cancer Study Grant award to MPH in 2003.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore