Histone deacetylase inhibitors: Anticancer compounds

The reversible acetylation of proteins is mediated by histone acetytransferases which acetylate proteins and historic deacetylases that remove the acetyl groups. High levels of histone acetylation are correlated with active genes, while hypoacetylation of histones corresponds with gone repression. Importantly, acetylation also occurs on non-histone proteins all this call affect the activity and stability of these proteins. Aberrant epigenetic changes ate a common hallmark Of tumors and Imbalances in the activities of deacetylases have been associated with cancers. Accordingly, inhibitors to the historic deacetylases are in clinical trials for the treatment of several cancer types. These drugs mediate a number Of molecular changes and ill turn Call induce cell cycle arrest, apoptosis or differentiation of cancer cells while displaying limited toxicity in normal cells. (C) 2003 Elsevier Ltd. All rights reserved.