Article (Scientific journals)
Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models
Depetter, Yves; Geurs, Silke; De Vreese, Rob et al.
2019In International Journal of Cancer
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Keywords :
Cancer; metabolomics; HDAC6
Abstract :
[en] Our study investigates the biochemical and functional impact of selective histone deacetylase 6 (HDAC6) inhibitors, a promising class of novel therapeutics, in several cancer models. Selective HDAC6 inhibitors (Tubathian A, Tubastatin A, Tubacin and Ricolinostat) and a non-selective HDAC inhibitor (Vorinostat) were evaluated on cancer cell lines derived from multiple tumour types in both an in vitro and in vivo setting as potential cancer therapeutics. Selective HDAC6 inhibitors resulted in α-tubulin acetylation with no impact on histone acetylation but failed to show any anti-cancer properties. Only the use of high concentrations of selective HDAC6 inhibitors resulted in co-inhibition of other HDAC enzymes and consequently in reduced growth, migratory and/or invasive activity of cancer cells in vitro as well as in vivo. The specificity of HDAC6 inhibition was confirmed using a CRISPR/Cas9 knockout cell line. Our results suggest that selective HDAC6 inhibitors may fall short as potential single agent anti-cancer drugs and prove that many previous data regarding this promising class of compounds need to be interpreted with great care due to their use in high concentrations resulting in low selectivity and potential off-target effects.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Depetter, Yves;  Ghent University > Green chemistry
Geurs, Silke;  Ghent University > Green chemistry
De Vreese, Rob;  Ghent University > Human structure and repair > Experimental Cancer Research
Goethals, Sophie;  Ghent university > Human structure and Repair > Experimental Cancer Research
Vandoorn, Elien;  Ghent University > Human structure and repair > Experimental Cancer Research
Steenbrugge, Jonas;  Ghent University > Human structure and Repair > Experimental Cancer Research
Meyer, Evelyne;  Cancer Research Institute
De Tullio, Pascal ;  Université de Liège - ULiège > CIRM > Metabolomics group
Bracke, Marc;  Cancer Research Institute Ghent
D'Hooghe, Matthias;  Ghent University > Green Chemistry
De Wever, Olivier;  Cancer Research Institute Ghent
Language :
English
Title :
Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models
Publication date :
2019
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 24 April 2019

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