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Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells Martínez Escardó, Laura Alemany, Montse Sánchez Osuna, María Sánchez Chardi, Alejandro Roig Martínez, Meritxell Suárez García, Salvio Ruiz Molina, Daniel Vidal, Noemí Plans, Gerard Majós Torró, Carlos Ribas, Judit Baltrons, Maria Antonia Bayascas, Jose R. Barcia, Carlos Bruna, Jordi Yuste, Victor J. Apoptosi Tumors cerebrals Apoptosis Brain tumors 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. 2021-12-13T12:02:15Z 2021-12-13T12:02:15Z 2021-11-08 2021-12-10T09:49:25Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.3390/cancers13215579 Cancers, 2021, vol. 13, num. 21, p. 5579 https://doi.org/10.3390/cancers13215579 cc by (c) Martínez Escardó, Laura et al, 2021 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess MDPI AG Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))