Histone deacetylase inhibitors: anticancer compounds.
The reversible acetylation of proteins is mediated by histone acetyltransferases which acetylate proteins and histone deacetylases that remove the acetyl groups. High levels of histone acetylation are correlated with active genes, while hypoacetylation of histones corresponds with gene repression. Importantly, acetylation also occurs on non-histone proteins and this can affect the activity and stability of these proteins. Aberrant epigenetic changes are a common hallmark of tumors and imbalances in the activities of deacetylases have been associated with cancers. Accordingly, inhibitors to the histone deacetylases are in clinical trials for the treatment of several cancer types. These drugs mediate a number of molecular changes and in turn can induce cell cycle arrest, apoptosis or differentiation of cancer cells while displaying limited toxicity in normal cells.
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Karen T
KT
Smith
Jerry L
JL
Workman
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases