Molecular Cancer apeutics linical Development one Deacetylase Inhibition Attenuates Cell Growth with ociated Telomerase Inhibition in High-Grade Ther ldhood Brain Tumor Cells

ownload rrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as anticancer agents. However, the mechanism of HDACi action with respect to the temporal order of d cellular events is unclear. The present study investigates the anticancer effects of the HDACi trichosin high-grade childhood brain tumor cells. Acute exposure to trichostatin A resulted in marked inhiof cell proliferation, an increase in the proportion of G2-M cells, activation of H2A.X, and subsequent ion of apoptosis in the majority of cell lines. These phenotypic effects were associated with abrogation merase activity and human telomerase reverse transcriptase downregulation in the majority of cell In contrast, no cytotoxicity was observed in primary ependymal cells with respect to cilia function. inhibition of histone deacetylases leads to antiproliferative and proapoptotic effects in childhood brain Thus, tumor cells, likely to involve altered chromatin regulation at the human telomerase reverse transcriptase promoter. Mol Cancer Ther; 9(9); 2568–81. ©2010 AACR.