Many plant-derived compounds are shown to be promising antitumor therapeutic agents by enhancing apoptosis-related pathways and cell cycle impairment in tumor cells, including glioblastoma (GBM) cell lines. We aimed to review four natural plant compounds effective in GBM cell lines as caffeine, dipotassium glycyrrhizinate (DPG), curcumin, and euphol. Furthermore, antitumoral effect of these plant compounds on GBM cell lines through microRNAs (miRs) modulation was investigated. However, only DPG and curcumin were found as effective on miR modulation. Caffeine arrests GBM cell cycle in G0/G1 phase by cyclin-dependent kinases (CDK) complex inhibition and by decreasing BCL-2 and increasing FOXO1 expression levels causing greater apoptotic activity. Caffeine can also directly inhibit IP3R3, p38 phosphorylation, and rho-associated protein kinase (ROCK), decreasing cell invasion and migration capacity or indirectly by inhibiting the tissue inhibitor metalloproteinase-1 (TIMP-1) and integrins β1 and β3, leading to lower matrix metalloproteinases, MMP-2 and MMP-9. DPG presents antitumoral effect in GBM cells related to nuclear factor kappa B (NF-κB) pathway suppression by IRAK2 and TRAF6-mediating miR-16 and miR-146a, respectively. More recently, it was observed that DPG upregulated miR-4443 and miR-3620, responsible for post-transcriptional inhibition of the NF-κB pathway by CD209 and TNC modulation, respectively leading to lower MMP-9 and migration capacity. Curcumin is able to increase miR-223-3p, miR-133a-3p, miR-181a-5p, miR-34a-5p, miR-30c-5p, and miR-1290 expression leading to serine or threonine kinase (AKT) pathway impairment and also it decreases miR-27a-5p, miR-221-3p, miR-21-5p, miR-125b-5p, and miR-151-3p expression causing p53-BCL2 pathway inhibition and consequently, cellular apoptosis. Interestingly, lower expression of miR-27a by curcumin action enhanced the C/EBP homologous protein(CHOP) expression, leading to paraptosis. Curcumin can inhibit miR-21 expression and consequently activate apoptosis through caspase 3 and death receptor (DR) 4 and 5 activation. Autophagy is controlled by the LC-3 protein that interacts with Atg family for the LC3-II formation and autophagy activation. Euphol can enhance LC3-II levels directly in GBM cells or inhibits tumor invasion and migration through PDK1 modulation.
Introdução: Plasmocitomas solitários (PS) são tumores sólidos, originados da proliferação local de linfócitos B maduros, que adquirem um padrão de multiplicação monoclonal e desordenado, correspondendo a 5% de todos os tumores de células plasmáticas. Quando não há evidência de discrasia plasmocitária em outros locais do corpo, o crânio e o sistema nervoso central são raramente afetados de maneira isolada por esse tipo de tumor, dificultando a realização de seu diagnóstico, sendo apenas definitivo através de exames imuno-histoquímicos e histopatológicos. Objetivo: O presente relato teve como objetivo reportar um caso raro de PS ósseo (PSO) em região cranioencefálica occipital, de importante significância clínica frente à escassez de relatos semelhantes existentes na literatura nacional e mundial. Resultados: Paciente de 78 anos encaminhado ao Hospital devido a abaulamento de crescimento progressivo em região occipital, mas consciente, orientado e sem déficits neurológicos focais. A tomografia computadorizada (TC) e angio-TC de crânio evidenciaram lesão expansiva sólida extra-axial com destruição óssea da calvária occipitoparietal. Foi realizada ressecção subtotal da lesão, tendo sido observada marcação para CD138, antígeno de plasmócitos MI15 (+), cadeia leve de imunoglobulina Kappa 18B5 (+), Lambda (-) e S-100 (-), confirmando o diagnóstico de PSO em região cranioencefálica occipital. O paciente obteve recuperação completa e, após um ano, evoluiu a óbito devido a complicações cardiovasculares. Conclusões: PSO é uma discrasia de células plasmáticas rara, mais comum em homens acima de 40 anos. A excisão cirúrgica do tumor faz parte de uma excelente medida primária. Portanto, conhecer aspectos clínicos garante o sucesso diagnóstico, visto a real probabilidade de evolução para mieloma múltiplo ou metástases.
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