2026-04-17T03:01:56Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/726112024-12-05T22:45:07Zcom_2072_3622col_2072_479130

00925njm 22002777a 4500 dc Martínez Escardó, Laura author Alemany, Montse author Sánchez Osuna, María author Sánchez Chardi, Alejandro author Roig Martínez, Meritxell author Suárez García, Salvio author Ruiz Molina, Daniel author Vidal, Noemí author Plans, Gerard author Majós, Carles author Ribas i Fortuny, Judit author Baltrons, María Antonia author Bayascas Ramírez, José Ramón author Barcia, Carlos author Bruna, Jordi author Yuste Mateos, Víctor J. (Víctor José) author 2021-12-21T12:36:20Z 2021-12-21T12:36:20Z 2021 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. 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). http://hdl.handle.net/10459.1/72611 Apoptosis Caspase-activated DNase (DFF40/CAD) Glioblastoma (GBM) Gossypol Nuclear fragmentation/disassembly Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells