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dc.contributor.author
Wagner, Paula Micaela
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dc.contributor.author
Monjes, Natalia Maribel
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dc.contributor.author
Guido, Mario Eduardo
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dc.date.available
2021-03-25T13:08:44Z
dc.date.issued
2019-12
dc.identifier.citation
Wagner, Paula Micaela; Monjes, Natalia Maribel; Guido, Mario Eduardo; Chemotherapeutic Effect of SR9009, a REV-ERB Agonist, on the Human Glioblastoma T98G Cells; SAGE Publications Inc.; ASN Neuro; 11; 12-2019; 1-14
dc.identifier.uri
http://hdl.handle.net/11336/128903
dc.description.abstract
Glioblastoma multiforme is the most aggressive brain tumor, and human T98G cells constitute a useful glioblastoma multiforme model to evaluate the chemotherapeutic agents. Modern life (shiftwork, jetlag, etc.) may cause circadian disorganization promoting higher cancer risk and metabolic disorders. Although little is known about the tumor-intrinsic circadian clock function, pharmacological modulation of circadian components may offer selective anticancer strategies. REV-ERBs are heme-binding circadian clock components acting as repressors of processes involved in tumorigenesis such as metabolism, proliferation, and inflammation. A synthetic pyrrole derivative (SR9009) that acts as REV-ERBs-specific agonists exhibits potent in vivo activity on metabolism and tumor cell viability. Here, we investigated SR9009 effects on T98G cell viability, differential chemotherapy time responses, and underlying metabolic processes (reactive oxygen species [ROS] and lipid droplets [LDs]) and compared it with the proteasome inhibitor Bortezomib treatment. SR9009-treated cells exhibited significant reduction in cell viability with consequences on cell cycle progression. Dexamethasone synchronized cells displayed differential time responses to SR9009 treatment with highest responses 18 to 30 h after synchronization. SR9009 treatment decreased ROS levels while Bortezomib increased them. However, both treatments significantly increased LD levels, whereas the combined treatment showed additive or synergistic effects between both drugs. In addition, we extended these studies to HepG2 cells which also showed a significant decrease in cell viability and ROS levels and the increase in LD levels after SR9009 treatment. Our results suggest that the pharmacological modulation of the tumor-intrinsic clock by REV-ERB agonists severely affects cell metabolism and promotes cytotoxic effects on cancer cells.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
SAGE Publications Inc.
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BORTEZOMIB
dc.subject
CLOCK GENE
dc.subject
GLIOBLASTOMA
dc.subject
LIPID DROPLET
dc.subject
REDOX STATE
dc.subject
REV-ERB
dc.subject
TUMOR CELL
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Chemotherapeutic Effect of SR9009, a REV-ERB Agonist, on the Human Glioblastoma T98G Cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-20T19:54:41Z
dc.identifier.eissn
1759-0914
dc.journal.volume
11
dc.journal.pagination
1-14
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Wagner, Paula Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
dc.description.fil
Fil: Monjes, Natalia Maribel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
dc.description.fil
Fil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
dc.journal.title
ASN Neuro
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1177/1759091419892713
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/1759091419892713
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