Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells
| Autor: | Victor J. Yuste, Daniel Ruiz-Molina, María Sánchez-Osuna, Carles Majós, Carlos Barcia, Noemi Vidal, Meritxell Roig-Martínez, Laura Martínez-Escardó, Montse Alemany, Alejandro Sánchez-Chardi, Gerard Plans, Judit Ribas, Salvio Suárez-García, María Antonia Baltrons, Jordi Bruna, Jose R. Bayascas |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, European Commission, Universidad Autónoma de Barcelona |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Programmed cell death DNA damage Apoptosis Brain tumors Article chemistry.chemical_compound Glioblastoma (GBM) medicine Tumors cerebrals Staurosporine Nuclear fragmentation/disassembly Fragmentation (cell biology) RC254-282 Caspase-activated DNase (DFF40/CAD) apoptosis Gossypol Neoplasms. Tumors. Oncology. Including cancer and carcinogens Apoptosi gossypol Chromatin Cytosol Oncology chemistry nuclear fragmentation/disassembly Cancer research glioblastoma (GBM) caspase-activated DNase (DFF40/CAD) medicine.drug |
| Zdroj: | Repositorio Abierto de la UdL Universitad de Lleida Cancers Digital.CSIC. Repositorio Institucional del CSIC instname Dipòsit Digital de la UB Universidad de Barcelona Cancers, Vol 13, Iss 5579, p 5579 (2021) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Volume 13 Issue 21 |
| Popis: | 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). With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001214-S) |
| Databáze: | OpenAIRE |
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