Histone deacetylase inhibitors: anticancer compounds

Int J Biochem Cell Biol. 2009 Jan;41(1):21-5. doi: 10.1016/j.biocel.2008.09.008. Epub 2008 Sep 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Cycle
  • Cell Differentiation
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • Histone Deacetylases