Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe

Thumbnail
View/Open
Issue date
2014-10-02
Author
Cornago Protomártir, Marta
Garcia-Alberich, C.
Blasco Angulo, Natividad
Vall-llaura Espinosa, Núria
Nàger Grifo, Mireia
Herreros Danés, Judit
Comella i Carnicé, Joan Xavier
Sanchis, Daniel
Llovera i Tomàs, Marta
Suggested citation
Cornago Protomártir, Marta; Garcia-Alberich, C.; Blasco Angulo, Natividad; Vall-llaura Espinosa, Núria; Nàger Grifo, Mireia; Herreros Danés, Judit; ... Llovera i Tomàs, Marta. (2014) . Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe. Cell Death & Disease, 2014, vol. 5, p. e1435. https://doi.org/10.1038/cddis.2014.412.
Impact

Google Scholar logo  Google Scholar
Share
Export to Mendeley
Metadata
Show full item record
Abstract
Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in
patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis.
URI
http://hdl.handle.net/10459.1/48735
DOI
https://doi.org/10.1038/cddis.2014.412
Is part of
Cell Death & Disease, 2014, vol. 5, p. e1435
Collections

The following license files are associated with this item:

cc-by-nc-sa (c) Macmillan Publishers Limited, 2014
Except where otherwise noted, this item's license is described as cc-by-nc-sa (c) Macmillan Publishers Limited, 2014