Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology

Impact factor: 3.6 (2023)

Detalles Bibliográficos
Autores principales: Wagner, Paula M., Fornasier E., Santiago J., Guido, Mario
Otros Autores: https://orcid.org/0000-0002-5485-4904
Formato: publishedVersion article
Lenguaje:Inglés
Publicado: 2024
Materias:
Acceso en línea: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.
Aporte de:
id I10-R141-11086-552641
record_format dspace
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-141
collection Repositorio Digital Universitario (UNC)
language Inglés
topic Circadian rhythm
Glioblastoma
Chronotherapy
Metabolic oscillator
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
topic_facet Circadian rhythm
Glioblastoma
Chronotherapy
Metabolic oscillator
description Impact factor: 3.6 (2023)
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
format publishedVersion
article
author Wagner, Paula M.
Fornasier E., Santiago J.
Guido, Mario
author_sort Wagner, Paula M.
title Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology
title_short 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_sort pharmacological modulation of the cytosolic oscillator afects glioblastoma cell biology
publishDate 2024
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.
work_keys_str_mv AT wagnerpaulam pharmacologicalmodulationofthecytosolicoscillatorafectsglioblastomacellbiology
AT fornasieresantiagoj pharmacologicalmodulationofthecytosolicoscillatorafectsglioblastomacellbiology
AT guidomario pharmacologicalmodulationofthecytosolicoscillatorafectsglioblastomacellbiology
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spelling I10-R141-11086-5526412024-07-09T06:23:22Z 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/