Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment

Citation
Uh. Weidle et A. Grossmann, Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment, ANTICANC R, 20(3A), 2000, pp. 1471-1485
Citations number
128
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ANTICANCER RESEARCH
ISSN journal
0250-7005 → ACNP
Volume
20
Issue
3A
Year of publication
2000
Pages
1471 - 1485
Database
ISI
SICI code
0250-7005(200005/06)20:3A<1471:IOHDAN>2.0.ZU;2-1
Abstract
The role of epigenetic modifications due to deregulated acetylation of nucl eosomes with respect to its role in progression and etiology of human cance r is discussed. Among the mediators of these phenomena are the histone deac etylases, a class of enzymes consisting of at least two subfamilies with a total of at least 7 members in mammals. Depending on the cell-type, inhibit ion of HDACs in cancer cells can lead to transcriptional activation and sil encing of about 2% of human genes, cell-cycle arrest and induction of apopt osis and differentiation in vitro and in vivo. This paper discusses several inhibitors of HDACs primarily derived from natural sources, their physiolo gical consequences in different in vitro and in vivo cancer-related systems , their stage of preclinical and clinical development as well as their pote ntial as antineoplastic agents. It is of paramount importance to elucidate the molecular mechanisms resulting in cell-cycle arrest, apoptosis ar diffe rentiation after inhibition of HDACs and to investigate the physiological f unction of the different HDAC isoenzymes and their deregulation in human ca ncels in order to devise optimized therapeutic intervention in cancer patie nts.