Histone Deacetylase Inhibitors in the Treatment of Hematological Malignancies and Solid Tumors
Mechanism of action of histone deacetylases inhibitors. It has been proposed that there are specific sites in the promoter region of a subset of genes that recruit the transcription factor complex (TFC) with histone deacetylases (HDACs). With inhibition of HDACs by HDACs inhibitors, histones are acetylated, and the DNA that is tightly wrapped around a deacetylated histone core relaxes. The accumulation of acetylated histones in nucleosomes leads to increased transcription of this subset of genes, which, in turn leads to downstream effects that result in cell-growth arrest, differentiation, and/or apoptosis.