Flavonoids from the Brazilian plant Croton betulaster inhibit the growth of human glioblastoma cells and induce apoptosis

Abstract This study investigated the effects of the flavonoids 5-hydroxy-7,4′-dimethoxyflavone, casticin, and penduletin, isolated from Croton betulaster Müll Arg., Euphorbiaceae, a plant utilized in popular medicine in Brazil, on the growth and viability of the human glioblastoma cell line GL-15. We observed that 5-hydroxy-7,4′-dimethoxyflavone and casticin were not toxic to GL-15 cells after 24 h of exposure. However, casticin and penduletin inhibited the metabolic activity of glioblastoma cells significantly at a concentration of 10 µM (p ≤ 0.05). Flavonoids casticin and penduletin also induced a significant and dose-dependent growth inhibition beginning at 24 h of exposure, and the most potent flavonoid was penduletin. It was also observed that penduletin and casticin induced an enlargement of the cell body and a reduction of cellular processes, accompanied by changes in the pattern of expression of the cytoskeletal protein vimentin. Signs of apoptosis, such as the externalization of membrane phosphatidyl serine residues, nuclear condensation, and fragmentation, were also detected in cells treated with 50–100 µM flavonoids. Our results indicate that flavonoids extracted from C. betulaster present antitumoral activity to glioblastoma cells, with penduletin proving to be the most potent of the tested flavonoids. Our results also suggest that these molecules may be promising supplementary drugs for glioblastoma treatment.

Pesquisa de interferon gama em tecido periodontal de ratos submetidos à movimentação dentária induzida / Gamma-interferon investigation in rat periodontal tissue under induced dental movement

INTRODUÇÃO: durante o tratamento ortodôntico, um processo inflamatório é induzido, desencadeando uma série de eventos bioquímicos que resultam na movimentação dentária. Estímulos como a hipóxia e a deformação mecânica são os principais fatores responsáveis pela quebra da homeostasia celular, resultando em estresse e liberação de diversos mediadores importantes para o movimento do dente. Para que a remodelação óssea ocorra durante o tratamento ortodôntico, fatores reguladores,como subprodutos do ácido araquidônico e citocinas,são liberados.Ao interferon gama (INF-γ , uma citocina principal liberada após a indução da resposta imune adaptativa, é atribuída a função de atrair os macrófagos, que auxiliam na remoção de restos celulares e promovem a cicatrização e reorganização das áreas com inflamação. OBJETIVO: visto que alguns aspectos biológicos que permeiam a movimentação dentária ainda não estão totalmente esclarecidos, procurou-se, neste trabalho, verificar a expressão do INF-γ por células do periodonto de ratos submetidos à movimentação ortodôntica. MÉTODOS: a amostra foi constituída por nove ratos, cujos primeiros molares superiores direitos foram movimentados com uma força de 0,5N, por 3, 7 e 14 dias. Os molares esquerdos desempenharam o papel de grupo controle. RESULTADOS: através da imunohistoquímica, foi verificada a ausência de expressão de INF-γ na quase totalidade dos tecidos estudados,tanto no lado de pressão quanto no lado de tração.

INTRODUCTION: During the orthodontic treatment, an inflammatory process is induced, triggering series of biochemical events that results in dental movement. Stimuli such as hypoxia and mechanical deformation are the main factors responsible for the breaking of cell homeostasis, resulting in stress and liberation of several important mediators for tooth movement. To occur osseous remodeling during orthodontic treatments, regulating factors such as sub products of arachidonic acid and cytokines are released. To interferon-gamma (INF-γ ), a main cytokine released after induction of adaptive immune response, is attributed the function of attracting the macrophages, which aids in removing cell rests and promote healing and reorganization of the inflamed areas. AIM: Given that some biological aspects that permeate dental movement are not yet fully clear, we aimed in this study to investigate INF-γ expression in the periodontium of rats under orthodontic movement. METHODS: The sample was composed of 9 rats, whose first upper right molars were moved with a force of 0,5N, for 3, 7 and 14 days. The left molars were used as controls. RESULTS: Through immunohistochemistry, we verified the absence of INF-γ expression in almost all the studied tissues, in both the traction and pressure sides.