Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile
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 flav...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/14/1/90 |
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| author | Irlã Santos Lima Érica Novaes Soares Carolina Kymie Vasques Nonaka Bruno Solano de Freitas Souza Balbino Lino dos Santos Silvia Lima Costa |
| author_facet | Irlã Santos Lima Érica Novaes Soares Carolina Kymie Vasques Nonaka Bruno Solano de Freitas Souza Balbino Lino dos Santos Silvia Lima Costa |
| author_sort | Irlã Santos Lima |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T11:03:21Z |
| format | Article |
| id | doaj.art-7b0516e7c4ad4a5cad5dcc7f25004d7b |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-08T11:03:21Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-7b0516e7c4ad4a5cad5dcc7f25004d7b2024-01-26T15:25:16ZengMDPI AGBrain Sciences2076-34252024-01-011419010.3390/brainsci14010090Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory ProfileIrlã Santos Lima0Érica Novaes Soares1Carolina Kymie Vasques Nonaka2Bruno Solano de Freitas Souza3Balbino Lino dos Santos4Silvia Lima Costa5Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, BrazilCenter of Biotechnology and Cell Therapy, São Rafael Hospital, D’Or Institute for Research and Teaching (IDOR), Salvador 41253-190, BrazilCenter of Biotechnology and Cell Therapy, São Rafael Hospital, D’Or Institute for Research and Teaching (IDOR), Salvador 41253-190, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, BrazilLaboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, BrazilGlioblastoma (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.https://www.mdpi.com/2076-3425/14/1/90glioblastomamiRNA-125bSTAT3inflammatory cytokinesrutin |
| spellingShingle | Irlã Santos Lima Érica Novaes Soares Carolina Kymie Vasques Nonaka Bruno Solano de Freitas Souza Balbino Lino dos Santos Silvia Lima Costa Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile Brain Sciences glioblastoma miRNA-125b STAT3 inflammatory cytokines rutin |
| title | Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile |
| title_full | Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile |
| title_fullStr | Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile |
| title_full_unstemmed | Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile |
| title_short | Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile |
| title_sort | flavonoid rutin presented anti glioblastoma activity related to the modulation of onco mirna 125b expression and stat3 signaling and impact on microglia inflammatory profile |
| topic | glioblastoma miRNA-125b STAT3 inflammatory cytokines rutin |
| url | https://www.mdpi.com/2076-3425/14/1/90 |
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