| Autor: |
Lima IS; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil., Soares ÉN; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil., Nonaka CKV; Center of Biotechnology and Cell Therapy, São Rafael Hospital, D'Or Institute for Research and Teaching (IDOR), Salvador 41253-190, Brazil., Souza BSF; Center of Biotechnology and Cell Therapy, São Rafael Hospital, D'Or Institute for Research and Teaching (IDOR), Salvador 41253-190, Brazil., Dos Santos BL; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil.; College of Nursing, Federal University of Vale do São Francisco, Petrolina 56304-917, Brazil., Costa SL; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil.; National Institute of Translation Neuroscience (INNT), Rio de Janeiro 21941-902, Brazil. |
| Abstrakt: |
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. |
