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dc.contributor.authorMartínez Escardó, Laura
dc.contributor.authorAlemany, Montse
dc.contributor.authorSánchez Osuna, María
dc.contributor.authorSánchez Chardi, Alejandro
dc.contributor.authorRoig Martínez, Meritxell
dc.contributor.authorSuárez García, Salvio
dc.contributor.authorRuiz Molina, Daniel
dc.contributor.authorVidal, Noemí
dc.contributor.authorPlans, Gerard
dc.contributor.authorMajós, Carles
dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorBaltrons, María Antonia
dc.contributor.authorBayascas Ramírez, José Ramón
dc.contributor.authorBarcia, Carlos
dc.contributor.authorBruna, Jordi
dc.contributor.authorYuste Mateos, Víctor J. (Víctor José)
dc.date.accessioned2021-12-21T12:36:20Z
dc.date.available2021-12-21T12:36:20Z
dc.date.issued2021
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10459.1/72611
dc.description.abstractGlioblastoma (GBM) is a highly aggressive brain tumor and almost all patients die because of relapses. GBM-derived cells undergo cell death without nuclear fragmentation upon treatment with different apoptotic agents. Nuclear dismantling determines the point-of-no-return in the apoptotic process. DFF40/CAD is the main endonuclease implicated in apoptotic nuclear disassembly. To be properly activated, DFF40/CAD should reside in the cytosol. However, the endonuclease is poorly expressed in the cytosol and remains cumulated in the nucleus of GBM cells. Here, by employing commercial and non-commercial patient-derived GBM cells, we demonstrate that the natural terpenoid aldehyde gossypol prompts DFF40/CAD-dependent nuclear fragmentation. A comparative analysis between gossypol- and staurosporine-treated cells evidenced that levels of neither caspase activation nor DNA damage were correlated with the ability of each compound to induce nuclear fragmentation. Deconvoluted confocal images revealed that DFF40/CAD was almost completely excluded from the nucleus early after the staurosporine challenge. However, gossypol-treated cells maintained DFF40/CAD in the nucleus for longer times, shaping a ribbon-like structure piercing the nuclear fragments and building a network of bridged masses of compacted chromatin. Therefore, GBM cells can fragment their nuclei if treated with the adequate insult, making the cell death process irreversible.ca_ES
dc.description.sponsorshipThis work was supported by grants SAF2017-83206-R funded by MCIN/Government of Spain (to V.J.Y.), SLT008/18/00028 from the CERCA Program/Generalitat de Catalunya (to J.B.), PGC2018-096003-B-I00 funded by MCI/AEI/10.130339/501100011033 and by ERDF A way of making Europe (to C.B.), and RTI2018-098027-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe (to D.R.-M.). The ICN2 is supported by the Severo Ochoa Centres of Excellence Program, grant SEV-2017-0706 funded by MCIN/AEI/10.13039/501100011033. The ICN2 is under the CERCA Program/Generalitat de Catalunya. L.M.-E. was recipient of a “Personal Investigador en Formació” fellow (BQ-2016-2) from Universitat Autònoma de Barcelona, and later supported by Oncobell program (IDIBELL).ca_ES
dc.language.isoengca_ES
dc.publisherMDPIca_ES
dc.relationMINECO/PN2013-2016/RTI2018-094222-B-I00ca_ES
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.3390/cancers13215579ca_ES
dc.relation.ispartofCancers 2021, vol. 13, núm. 21, 5579ca_ES
dc.rightscc-by (c) authors, 2021ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectApoptosisca_ES
dc.subjectCaspase-activated DNase (DFF40/CAD)ca_ES
dc.subjectGlioblastoma (GBM)ca_ES
dc.subjectGossypolca_ES
dc.subjectNuclear fragmentation/disassemblyca_ES
dc.titleGossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cellsca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.identifier.idgrec031650
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.3390/cancers13215579


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