Cytotoxicity mediated by histone deacetylase inhibitors in cancer cells: mechanisms and potential clinical implications.
Aberrant expression of epigenetic regulators of gene expression contributes to initiation and progression of cancer. During recent years, considerable research efforts have focused on the role of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in cancer cells, and the identification of pharmacologic agents that modulate gene expression via inhibition of HDACs. The following review highlights recent studies pertaining to HDAC expression in cancer cells, the plieotropic mechanisms by which HDAC inhibitors (HDACi) mediate antitumor activity, and the potential clinical implications of HDAC inhibition as a strategy for cancer therapy.
Schrump
David S
DS
Thoracic Oncology Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-1201, USA. david_schrump@nih.gov
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001343:Autophagy; D019175:DNA Methylation / Q000187:drug effects; D047630:Depsipeptides / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C087123:romidepsin; D051548:Histone Acetyltransferases