Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology

Autores
Wagner, Paula M.; Fornasier E., Santiago J.; Guido, Mario
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Impact factor: 3.6 (2023)
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.
Materia
Circadian rhythm
Glioblastoma
Chronotherapy
Metabolic oscillator
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Repositorio Digital Universitario (UNC)
Institución
Universidad Nacional de Córdoba
OAI Identificador
oai:rdu.unc.edu.ar:11086/552641
Acceder
id RDUUNC_2f4b8774702b658cc0fa5c3e044ed2cb
oai_identifier_str oai:rdu.unc.edu.ar:11086/552641
network_acronym_str RDUUNC
repository_id_str 2572
network_name_str Repositorio Digital Universitario (UNC)
spelling Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell BiologyWagner, Paula M.Fornasier E., Santiago J.Guido, MarioCircadian rhythmGlioblastomaChronotherapyMetabolic oscillatorImpact factor: 3.6 (2023)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/publishedVersionFil: 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.https://orcid.org/0000-0002-5485-49042024-06-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfWagner, 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/11086/5526411573-6830https://link.springer.com/article/10.1007/s10571-024-01485-2https://doi.org/10.1007/s10571-024-01485-2.enginfo:eu-repo/semantics/openAccessreponame:Repositorio Digital Universitario (UNC)instname:Universidad Nacional de Córdobainstacron:UNC2025-10-23T11:19:00Zoai:rdu.unc.edu.ar:11086/552641Institucionalhttps://rdu.unc.edu.ar/Universidad públicaNo correspondehttp://rdu.unc.edu.ar/oai/snrdoca.unc@gmail.comArgentinaNo correspondeNo correspondeNo correspondeopendoar:25722025-10-23 11:19:00.848Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdobafalse
dc.title.none.fl_str_mv Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology
title Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology
spellingShingle Pharmacological Modulation of the Cytosolic Oscillator Afects Glioblastoma Cell Biology
Wagner, Paula M.
Circadian rhythm
Glioblastoma
Chronotherapy
Metabolic oscillator
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
dc.creator.none.fl_str_mv Wagner, Paula M.
Fornasier E., Santiago J.
Guido, Mario
author Wagner, Paula M.
author_facet Wagner, Paula M.
Fornasier E., Santiago J.
Guido, Mario
author_role author
author2 Fornasier E., Santiago J.
Guido, Mario
author2_role author
author
dc.contributor.none.fl_str_mv https://orcid.org/0000-0002-5485-4904
dc.subject.none.fl_str_mv Circadian rhythm
Glioblastoma
Chronotherapy
Metabolic oscillator
topic Circadian rhythm
Glioblastoma
Chronotherapy
Metabolic oscillator
dc.description.none.fl_txt_mv Impact factor: 3.6 (2023)
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.
description Impact factor: 3.6 (2023)
publishDate 2024
dc.date.none.fl_str_mv 2024-06-22
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
status_str publishedVersion
format article
dc.identifier.none.fl_str_mv 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.
identifier_str_mv 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.
1573-6830
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.
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositorio Digital Universitario (UNC)
instname:Universidad Nacional de Córdoba
instacron:UNC
reponame_str Repositorio Digital Universitario (UNC)
collection Repositorio Digital Universitario (UNC)
instname_str Universidad Nacional de Córdoba
instacron_str UNC
institution UNC
repository.name.fl_str_mv Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdoba
repository.mail.fl_str_mv oca.unc@gmail.com
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score 12.982451

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