Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology
Impact factor: 3.6 (2023)
| Main Authors: | , , |
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| Format: | info:eu-repo/semantics/publishedVersion |
| Language: | eng |
| Published: |
2024
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| Online Access: | http://hdl.handle.net/11086/552641 https://link.springer.com/article/10.1007/s10571-024-01485-2 https://doi.org/10.1007/s10571-024-01485-2. |
| _version_ | 1806012472486789120 |
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| author | Wagner, Paula M. Fornasier E., Santiago J. Guido, Mario |
| author2 | https://orcid.org/0000-0002-5485-4904 |
| author_facet | https://orcid.org/0000-0002-5485-4904 Wagner, Paula M. Fornasier E., Santiago J. Guido, Mario |
| author_sort | Wagner, Paula M. |
| collection | Repositorio Digital Universitario |
| description | Impact factor: 3.6 (2023) |
| format | info:eu-repo/semantics/publishedVersion |
| id | rdu-unc.552641 |
| institution | Universidad Nacional de Cordoba |
| language | eng |
| publishDate | 2024 |
| record_format | dspace |
| spelling | rdu-unc.5526412024-07-09T06:23:22Z Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology Wagner, Paula M. Fornasier E., Santiago J. Guido, Mario https://orcid.org/0000-0002-5485-4904 Circadian rhythm Glioblastoma Chronotherapy Metabolic oscillator Impact factor: 3.6 (2023) info:eu-repo/semantics/publishedVersion Fil: Wagner, Paula M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto, Argentina. Fil: Wagner, Paula M. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Fornasier, Santiago J. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto, Argentina. Fil: Fornasier, Santiago J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Guido, Mario E. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto, Argentina. Fil: Guido, Mario E. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12–15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology. info:eu-repo/semantics/publishedVersion Fil: Wagner, Paula M. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto, Argentina. Fil: Wagner, Paula M. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Fornasier, Santiago J. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto, Argentina. Fil: Fornasier, Santiago J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. Fil: Guido, Mario E. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto, Argentina. Fil: Guido, Mario E. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina. 2024-07-08T20:54:54Z 2024-07-08T20:54:54Z 2024-06-22 article Wagner, P. M., Fornasier, S. J., & Guido, M. E. (2024). Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology. Cellular and Molecular Neurobiology, 44(1), 51. http://hdl.handle.net/11086/552641 1573-6830 https://link.springer.com/article/10.1007/s10571-024-01485-2 https://doi.org/10.1007/s10571-024-01485-2. eng Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | Circadian rhythm Glioblastoma Chronotherapy Metabolic oscillator Wagner, Paula M. Fornasier E., Santiago J. Guido, Mario Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology |
| title | Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology |
| title_full | Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology |
| title_fullStr | Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology |
| title_full_unstemmed | Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology |
| title_short | Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology |
| title_sort | pharmacological modulation of the cytosolic oscillator afects glioblastoma cell biology |
| topic | Circadian rhythm Glioblastoma Chronotherapy Metabolic oscillator |
| url | http://hdl.handle.net/11086/552641 https://link.springer.com/article/10.1007/s10571-024-01485-2 https://doi.org/10.1007/s10571-024-01485-2. |
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