Document Detail


HDAC11 is a novel drug target in carcinomas.
MedLine Citation:
PMID:  23024001     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Inhibition of histone deacetylase (HDAC) activity as stand-alone or combination therapy represents a promising therapeutic approach in oncology. The pan- or class I HDAC-inhibitors (HDACi) currently approved or in clinical studies for oncology give rise to dose-limiting toxicities, presumably due to the inhibition of several HDACs. This could potentially be overcome by selective blockade of single HDAC family members. Here we report that HDAC11, the most recently identified zinc-dependent HDAC, is overexpressed in several carcinomas compared to corresponding healthy tissues. HDAC11 depletion is sufficient to cause cell death and to inhibit metabolic activity in HCT-116 colon, PC-3 prostate, MCF-7 breast and SK-OV-3 ovarian cancer cell lines. The anti-tumoral effect induced can be mimicked by enforced expression of a catalytically impaired HDAC11 variant, suggesting that inhibition of the enzymatic activity of HDAC11 by small molecules could trigger the desired phenotypic changes. HDAC11 depletion in normal cells causes no changes in metabolic activity and viability, strongly suggesting that tumor-selective effects can be achieved. Altogether, our data show that HDAC11 plays a critical role in cancer cell survival and may represent a novel drug target in oncology. © 2012 Wiley-Liss, Inc.
Authors:
Hedwig E Deubzer; Marie C Schier; Ina Oehme; Marco Lodrini; Bernard Haendler; Anette Sommer; Olaf Witt
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 UICC.
Affiliation:
Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Hematology and Oncology, University of Heidelberg, Heidelberg, Germany. h.deubzer@dkfz.de.
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