Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells
| dc.contributor.author | Martínez Escardó, Laura | |
| dc.contributor.author | Alemany, Montse | |
| dc.contributor.author | Sánchez Osuna, María | |
| dc.contributor.author | Sánchez Chardi, Alejandro | |
| dc.contributor.author | Roig Martínez, Meritxell | |
| dc.contributor.author | Suárez García, Salvio | |
| dc.contributor.author | Ruiz Molina, Daniel | |
| dc.contributor.author | Vidal, Noemí | |
| dc.contributor.author | Plans, Gerard | |
| dc.contributor.author | Majós, Carles | |
| dc.contributor.author | Ribas i Fortuny, Judit | |
| dc.contributor.author | Baltrons, María Antonia | |
| dc.contributor.author | Bayascas Ramírez, José Ramón | |
| dc.contributor.author | Barcia, Carlos | |
| dc.contributor.author | Bruna, Jordi | |
| dc.contributor.author | Yuste Mateos, Víctor J. (Víctor José) | |
| dc.date.accessioned | 2021-12-21T12:36:20Z | |
| dc.date.available | 2021-12-21T12:36:20Z | |
| dc.date.issued | 2021 | |
| dc.identifier.issn | 2072-6694 | |
| dc.identifier.uri | http://hdl.handle.net/10459.1/72611 | |
| dc.description.abstract | Glioblastoma (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.sponsorship | This 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.iso | eng | ca_ES |
| dc.publisher | MDPI | ca_ES |
| dc.relation | MINECO/PN2013-2016/RTI2018-094222-B-I00 | ca_ES |
| dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3390/cancers13215579 | ca_ES |
| dc.relation.ispartof | Cancers 2021, vol. 13, núm. 21, 5579 | ca_ES |
| dc.rights | cc-by (c) authors, 2021 | ca_ES |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
| dc.subject | Apoptosis | ca_ES |
| dc.subject | Caspase-activated DNase (DFF40/CAD) | ca_ES |
| dc.subject | Glioblastoma (GBM) | ca_ES |
| dc.subject | Gossypol | ca_ES |
| dc.subject | Nuclear fragmentation/disassembly | ca_ES |
| dc.title | Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells | ca_ES |
| dc.type | info:eu-repo/semantics/article | ca_ES |
| dc.identifier.idgrec | 031650 | |
| dc.type.version | info:eu-repo/semantics/publishedVersion | ca_ES |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_ES |
| dc.identifier.doi | https://doi.org/10.3390/cancers13215579 |
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