HDAC11 is a novel drug target in carcinomas
- 25 October 2012
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 132 (9), 2200-2208
- https://doi.org/10.1002/ijc.27876
Abstract
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 because of 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 as 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 antitumoral 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.Keywords
This publication has 29 references indexed in Scilit:
- The role of peroxisome proliferator-activated receptors in carcinogenesis and chemopreventionNature Reviews Cancer, 2012
- Romidepsin: A Guide to its Clinical Use in Cutaneous T-Cell LymphomaAmerican Journal of Clinical Dermatology, 2012
- High-throughput detection and multiplex identification of cell contaminationsNucleic Acids Research, 2009
- Acetylation/Deacetylation Modulates the Stability of DNA Replication Licensing Factor Cdt1Published by Elsevier BV ,2009
- The many roles of histone deacetylases in development and physiology: implications for disease and therapyNature Reviews Genetics, 2009
- The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and menNature Reviews Molecular Cell Biology, 2008
- AK2 activates a novel apoptotic pathway through formation of a complex with FADD and caspase-10Nature, 2007
- Anticancer activities of histone deacetylase inhibitorsNature Reviews Drug Discovery, 2006
- Epigenetic therapy of cancer: past, present and futureNature Reviews Drug Discovery, 2006
- The Target Discovery ProcessChemBioChem, 2005