Martínez Escardó, LauraAlemany, MontseSánchez Osuna, MaríaSánchez Chardi, AlejandroRoig Martínez, MeritxellSuárez García, SalvioRuiz Molina, DanielVidal, NoemíPlans, GerardMajós Torró, CarlosRibas, JuditBaltrons, Maria AntoniaBayascas, Jose R.Barcia, CarlosBruna, JordiYuste, Victor J.2021-12-132021-12-132021-11-082072-6694https://hdl.handle.net/2445/181800Glioblastoma (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.18 p.application/pdfengcc by (c) Martínez Escardó, Laura et al, 2021http://creativecommons.org/licenses/by/3.0/es/ApoptosiTumors cerebralsApoptosisBrain tumorsinfo:eu-repo/semantics/article2021-12-10info:eu-repo/semantics/openAccess34771741