To access the full text documents, please follow this link: http://hdl.handle.net/10459.1/48735

Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe
Cornago Protomartir, Marta; Garcia-Alberich, C.; Blasco Angulo, Natividad; Vall-Llaura Espinosa, Núria; Nager Grifo, Mireia; Herreros Danes, Judit; Comella i Carnicé, Joan Xavier; Sanchis, Daniel; Llovera i Tomàs, Marta
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.
2014-10-02
Glioma
Cèl·lules
Gliomas
Cells
http://creativecommons.org/licenses/by-nc-sa/3.0/es
cc-by-nc-sa (c) Macmillan Publishers Limited, 2014
Article
Nature Publishing Group
         

Full text files in this document

Files Size Format View
021621.pdf 3.872 MB application/pdf View/Open

Show full item record

Related documents

Other documents of the same author

 

Coordination

 

Supporters