Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile
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Published:2024-01-17
Issue:1
Volume:14
Page:90
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ISSN:2076-3425
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Container-title:Brain Sciences
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language:en
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Short-container-title:Brain Sciences
Author:
Lima Irlã Santos1ORCID, Soares Érica Novaes1ORCID, Nonaka Carolina Kymie Vasques2ORCID, Souza Bruno Solano de Freitas2, dos Santos Balbino Lino13ORCID, Costa Silvia Lima14ORCID
Affiliation:
1. Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil 2. Center of Biotechnology and Cell Therapy, São Rafael Hospital, D’Or Institute for Research and Teaching (IDOR), Salvador 41253-190, Brazil 3. College of Nursing, Federal University of Vale do São Francisco, Petrolina 56304-917, Brazil 4. National Institute of Translation Neuroscience (INNT), Rio de Janeiro 21941-902, Brazil
Abstract
Glioblastoma (GBM) is the most aggressive and treatment-resistant brain tumor. In the GBM microenvironment, interaction with microglia is associated with the dysregulation of cytokines, chemokines, and miRNAs, contributing to angiogenesis, proliferation, anti-apoptosis, and chemoresistance. The flavonoid rutin can inhibit glioma cell growth associated with microglial activation and production of pro-inflammatory mediators by mechanisms that are still poorly understood. The present study investigated the effect of rutin on viability, regulation of miRNA-125b, and the STAT3 expression in GBM cells, as well as the effects on the modulation of the inflammatory profile and STAT3 expression in microglia during indirect interaction with GBM cells. Human GL15-GBM cells and human C20 microglia were treated or not with rutin for 24 h. Rutin (30–50 μM) significantly reduced the viability of GL15 cells; however, it did not affect the viability of microglia. Rutin (30 μM) significantly reduced the expression of miRNA-125b in the cells and secretome and STAT3 expression. Microglia submitted to the conditioned medium from GBM cells treated with rutin showed reactive morphology associated with reduced expression of IL-6, TNF, and STAT3. These results reiterate the anti-glioma effects of the flavonoid, which may also modulate microglia towards a more responsive anti-tumor phenotype, constituting a promising molecule for adjuvant therapy to GBM.
Funder
Coordination of Personnel Improvement of Higher Level National Council for Scientific and Technological Development
Subject
General Neuroscience
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