Teratogenic Activity of HDAC Inhibitors

ISSN: 1873-4286 (Online)
ISSN: 1381-6128 (Print)


Volume 20, 42 Issues, 2014


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Teratogenic Activity of HDAC Inhibitors

Author(s): Erminio Giavini and Elena Menegola

Affiliation: Università degli Studi di Milano, Department of Biosciences, via Celoria 26, I-20133 Milano, Italy

Abstract

Modification of the terminal tails of histones is considered one of the documented mechanism for epigenetic control of gene expression. Histone deacetylase inhibitors (HDACi) lead to a state of hyperacetylation of histone, a condition that can affect normal gene transcription. Furthermore, HDACi have many other protein targets involved in regulation of gene expression, cell proliferation and cell death. For these properties some HDACi are nowadays used as anticancer drugs with promising results. Several molecules with HDACi properties (valproic acid, trichostatin A, apicidin, MS-275, sodium butyrate, boric acid, salicylic acid) have been found to induce congenital malformations associated with hyperacetylation of histones in the target organs. Cell death is the major event in the target organs a few hours after embryonic exposure to HDACi. Gene deregulation, oxidative stress, DNA demethylation, and/or retinoic acid imbalance are the modes of action postulated for HDACi-induced teratogenesis

Keywords: HDAC inhibitors, teratogenesis, congenital malformations, mechanisms

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Article Details

Volume: 20
First Page: 1
Last Page: 5
Page Count: 5
DOI: 10.2174/1381612820666140205144900
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