Histone Deacetylase Inhibitors (HDI) cause DNA damage in leukemia cells : a mechanism for leukemia-specific HDI-dependent apoptosis?

Gaymes, Terry J., Padua, Rose Ann, Pla, Marika, Orr, Steven, Omidvar, Nader, Chomienne, Christine, Mufti, Ghulam J. and Rassool, Feyruz V. (2006) Histone Deacetylase Inhibitors (HDI) cause DNA damage in leukemia cells : a mechanism for leukemia-specific HDI-dependent apoptosis? Molecular Cancer Research, 4(8), pp. 563-573. ISSN (print) 1541-7786

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Abstract

Histone deacetylase inhibitors (HDI) increase gene expression through induction of histone acetylation. However, it remains unclear whether increases in specific gene expression events determine the apoptotic response following HDI administration. Herein, we show that a variety of HDI trigger in hematopoietic cells not only widespread histone acetylation and DNA damage responses but also actual DNA damage, which is significantly increased in leukemic cells compared with normal cells. Thus, increase in H2AX and ataxia telangiectasia mutated (ATM) phosphorylation, early markers of DNA damage, occurs rapidly following HDI administration. Activation of the DNA damage and repair response following HDI treatment is further emphasized by localizing DNA repair proteins to regions of DNA damage. These events are followed by subsequent apoptosis of neoplastic cells but not normal cells. Our data indicate that induction of apoptosis by HDI may result predominantly through accumulation of excessive DNA damage in leukemia cells, leading to activation of apoptosis.

Item Type: Article
Research Area: Biological sciences
Cancer studies
Chemistry
Faculty, School or Research Centre: Faculty of Science (until 2011) > School of Life Sciences
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Depositing User: Terry Gaymes
Date Deposited: 25 Aug 2017 13:26
Last Modified: 25 Aug 2017 13:26
URI: http://eprints.kingston.ac.uk/id/eprint/38263

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