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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-19961

Dedes, K J; Dedes, I; Imesch, P; von Bueren, A O; Fink, D; Fedier, A (2009). Acquired vorinostat resistance shows partial cross-resistance to 'second-generation' HDAC inhibitors and correlates with loss of histone acetylation and apoptosis but not with altered HDAC and HAT activities. Anti-Cancer Drugs, 20(5):321-333.

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Histone deacetylase (HDAC) inhibitors such as vorinostat (suberoylanilide hydroxamic acid), valproic acid, romidepsin (FK-228), and LBH589 comprise a relatively new class of potent anticancer agents. This study provides evidence for the potential of vorinostat to cause acquisition of multidrug resistance protein-independent resistance in HCT116 colon tumor cells. This acquired resistance is moderate (two-fold to three-fold), is nonreversible, and correlates with the loss of responses typically seen with HDAC inhibitors, that is the loss of acetylation of the histones H2A, H2B, H3, and H4, the loss of the G2/M checkpoint activation, and the loss of caspase 3-dependent and caspase 7-dependent apoptosis. This acquired resistance also associates with cross-resistance to the hydroxamate-class (LBH589 and JNJ26481585) and to the aliphatic acid-class (valproic acid) HDAC inhibitors but not to the benzamide-class (MGCD0103) and the cyclic peptide-class (romidepsin) HDAC inhibitors. The acquired HDAC inhibitor resistance described hereis not a result of altered HDAC and histone acetyltransferase activities and differs from that previously reported for romidepsin.


22 citations in Web of Science®
22 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
Dewey Decimal Classification:610 Medicine & health
Date:June 2009
Deposited On:29 Jul 2009 09:26
Last Modified:05 Apr 2016 13:18
Publisher:Lippincott Wiliams & Wilkins
Additional Information:This is a non-final version of an article published in final form in Anti-Cancer Drugs
Publisher DOI:10.1097/CAD.0b013e3283262a32
PubMed ID:19322073

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