dc.creatorWagner, Paula Micaela
dc.creatorMonjes, Natalia Maribel
dc.creatorGuido, Mario Eduardo
dc.date.accessioned2021-03-25T13:08:44Z
dc.date.accessioned2022-10-15T15:12:17Z
dc.date.available2021-03-25T13:08:44Z
dc.date.available2022-10-15T15:12:17Z
dc.date.created2021-03-25T13:08:44Z
dc.date.issued2019-12
dc.identifierWagner, 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.identifierhttp://hdl.handle.net/11336/128903
dc.identifier1759-0914
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4401163
dc.description.abstractGlioblastoma 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.languageeng
dc.publisherSAGE Publications Inc.
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1177/1759091419892713
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/1759091419892713
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBORTEZOMIB
dc.subjectCLOCK GENE
dc.subjectGLIOBLASTOMA
dc.subjectLIPID DROPLET
dc.subjectREDOX STATE
dc.subjectREV-ERB
dc.subjectTUMOR CELL
dc.titleChemotherapeutic Effect of SR9009, a REV-ERB Agonist, on the Human Glioblastoma T98G Cells
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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