Premium
Targeting histone deacetylase in cancer therapy
Author(s) -
Lin HsiangYu,
Chen ChangShi,
Lin ShuanPei,
Weng JingRu,
Chen ChingShih
Publication year - 2006
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20056
Subject(s) - histone deacetylase , acetylation , histone deacetylase 5 , histone , epigenetics , cancer research , biology , chromatin , hdac11 , chromatin remodeling , chemistry , microbiology and biotechnology , biochemistry , gene
Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer treatment as many HDAC inhibitors have entered clinical trials for both solid and liquid tumors. Nevertheless, the mechanisms underlying the antiproliferative effects of HDAC inhibitors remain elusive. Although they have been shown to regulate the transcription of a defined set of genes through chromatin remodeling, increasing evidence suggests that modifications of the epigenetic histone code may not be the primary mechanism for HDAC inhibitor‐mediated growth inhibition and apoptosis in cancer cells. While histones still represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcription‐independent mechanisms by modulating the acetylation status of a series of nonhistone targets. Also noteworthy is the effect of HDAC inhibitors on Akt downregulation through the alteration of protein phosphatase 1 (PP1) complex formation. To provide an overview of the use of HDAC inhibitors in cancer treatment, this review addresses the following subjects: (1) the physiological relevance of HDAC‐mediated acetylation of histone and nonhistone substrates, (2) the chemical biology of HDACs and development of a novel class of HDAC inhibitors, and (3) the protein acetylation‐independent effect of HDAC inhibitors on the activation status of signaling kinases. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 4, 397–413, 2006