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

View/ Open
Issue date
2014-10-02Author
Cornago Protomártir, Marta
Garcia-Alberich, C.
Blasco Angulo, Natividad
Comella i Carnicé, Joan Xavier
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.
Metadata
Show full item recordAbstract
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.
Is part of
Cell Death & Disease, 2014, vol. 5, p. e1435European research projects
Collections
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as cc-by-nc-sa (c) Macmillan Publishers Limited, 2014
Related items
Showing items related by title, author, creator and subject.
-
Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylation
David, Mónica Delia; Yeramian Hakim, Andree; Duñach, Mireia; Llovera i Tomàs, Marta; Cantí Nicolás, Carles; Garcia de Herreros, Antonio; Comella i Carnicé, Joan Xavier; Herreros Danés, Judit (Company of Biologist, 2008)Tyrosine phosphorylation of ß-catenin, a component of adhesion complexes and the Wnt pathway, affects cell adhesion, migration and gene transcription. By reducing ßcatenin availability using shRNA-mediated gene silencing ... -
EndoG links Bnip3-induced mitochondrial damage and caspase-independent DNA fragmentation in ischemic cardiomyocytes
Zhang, Jisheng; Ye, Junmei; Altafaj, Albert; Cardona Colom, Maria; Bahi i Pla, Núria; Llovera i Tomàs, Marta; Cañas, Xavier; Cook, Stuart A.; Comella i Carnicé, Joan Xavier; Sanchis, Daniel (Public Library of Science (PLoS), 2011)Mitochondrial dysfunction, caspase activation and caspase-dependent DNA fragmentation are involved in cell damage in many tissues. However, differentiated cardiomyocytes repress the expression of the canonical apoptotic ... -
BCL-XL regulates TNF-α-mediated cell death independently of NF-κB, FLIP and IAPs
Gozzelino, Raffaella; Solé Serra, Carme; Llecha Cano, Núria; Segura Ginard, Miguel Francisco; Moubarak, Rana S.; Iglesias Guimarais, Victoria; Pérez García, María José; Reix, Stéphanie; Zhang, Jisheng; Badiola, Nahuai; Sanchis, Daniel; Rodríguez Álvarez, José; Trullas, Ramon; Yuste Mateos, Víctor J. (Víctor José); Comella i Carnicé, Joan Xavier (Springer Nature, 2008)Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believed that ...