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dc.contributor.authorCornago Protomártir, Marta
dc.contributor.authorGarcia-Alberich, C.
dc.contributor.authorBlasco Angulo, Natividad
dc.contributor.authorVall-llaura Espinosa, Núria
dc.contributor.authorNàger Grifo, Mireia
dc.contributor.authorHerreros Danés, Judit
dc.contributor.authorComella i Carnicé, Joan Xavier
dc.contributor.authorSanchis, Daniel
dc.contributor.authorLlovera i Tomàs, Marta
dc.date.accessioned2015-09-22T12:51:25Z
dc.date.available2015-09-22T12:51:25Z
dc.date.issued2014-10-02
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/10459.1/48735
dc.description.abstractGlioblastoma 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.
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Health grant ISCIII and the European Fund for Regional Development (FEDER) PS09/00140 to ML, ISCIII-PI080790 to JH and Programa de Suport a Grups de Recerca from the Government of Catalonia (AGAUR) (2009-SGR-346) to ML, DS and JXC.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relationMICINN/PN2008-2011/PS09/00140
dc.relationMICINN/PN2008-2011/ISCIII-PI080790
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1038/cddis.2014.412
dc.relation.ispartofCell Death & Disease, 2014, vol. 5, p. e1435
dc.rightscc-by-nc-sa (c) Macmillan Publishers Limited, 2014
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/es
dc.subject.classificationGlioma
dc.subject.classificationCèl·lules
dc.subject.otherGliomas
dc.subject.otherCells
dc.titleHistone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2015-09-22T12:51:25Z
dc.identifier.idgrec021621
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1038/cddis.2014.412


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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