Histone deacetylase inhibitors: Potential in cancer therapy Journal Article
| Authors: | Marks, P. A.; Xu, W. S. |
| Article Title: | Histone deacetylase inhibitors: Potential in cancer therapy |
| Abstract: | The role of histone deacetylases (HDAC) and the potential of these enzymes as therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders is an area of rapidly expanding investigation. There are 18 HDACs in humans. These enzymes are not redundant in function. Eleven of the HDACs are zinc dependent, classified on the basis of homology to yeast HDACs: Class I includes HDACs 1, 2, 3, and 8; Class IIA includes HDACs 4, 5, 7, and 9; Class IIB, HDACs 6 and 10; and Class IV, HDAC 11. Class III HDACs, sirtuins 1-7, have an absolute requirement for NAD<sup>+</sup>, are not zinc dependent and generally not inhibited by compounds that inhibit zinc dependent deacetylases. In addition to histones, HDACs have many nonhistone protein substrates which have a role in regulation of gene expression, cell proliferation, cell migration, cell death, and angiogenesis. HDAC inhibitors (HDACi) have been discovered of different chemical structure. HDACi cause accumulation of acetylated forms of proteins which can alter their structure and function. HDACi can induce different phenotypes in various transformed cells, including growth arrest, apoptosis, reactive oxygen species facilitated cell death and mitotic cell death. Normal cells are relatively resistant to HDACi induced cell death. Several HDACi are in various stages of development, including clinical trials as monotherapy and in combination with other anti-cancer drugs and radiation. The first HDACi approved by the FDA for cancer therapy is suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza), approved for treatment of cutaneous T-cell lymphoma. © 2009 Wiley-Liss, Inc. |
| Keywords: | unclassified drug; fludarabine; histone deacetylase inhibitor; itf 2357; clinical trial; fatigue; review; angiogenesis inhibitor; cancer combination chemotherapy; diarrhea; drug potentiation; monotherapy; nonhuman; antineoplastic agents; gemcitabine; neoplasms; cell proliferation; phenotype; cell death; imatinib; carboplatin; unindexed drug; apoptosis; nausea; thrombocytopenia; dehydration; nucleoside analog; antineoplastic activity; drug structure; angiogenesis; protein tyrosine kinase inhibitor; gene expression regulation; cutaneous t cell lymphoma; enzyme inhibitors; vorinostat; cell migration; reactive oxygen metabolite; taxane derivative; anthracycline derivative; dna topoisomerase inhibitor; zinc; n (2 aminophenyl) 4 [4 (3 pyridinyl) 2 pyrimidinylaminomethyl]benzamide; panobinostat; romidepsin; histone deacetylases; azacitidine; valproic acid; histone deacetylase; 3 phenylsulfamoylcinnamohydroxamic acid; arylbutyric acid derivative; jhj 26481585; n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide; nicotinamide adenine dinucleotide; pc 24781; pivaloyloxymethyl butyrate; sb 939; sirtuin; vp 101; growth disorder; cell physiological processes |
| Journal Title: | Journal of Cellular Biochemistry |
| Volume: | 107 |
| Issue: | 4 |
| ISSN: | 0730-2312 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2009-07-01 |
| Start Page: | 600 |
| End Page: | 608 |
| Language: | English |
| DOI: | 10.1002/jcb.22185 |
| PUBMED: | 19459166 |
| PROVIDER: | scopus |
| PMCID: | PMC2766855 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 50" - "Export Date: 30 November 2010" - "CODEN: JCEBD" - "Source: Scopus" |
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