Abstract
This study investigated the effects of the flavonoids 5-hydroxy-7,4’-dimethoxyflavone, casticin, and pen-duletin, 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 24h 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.
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Acknowledgements
This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil (CNPq — 470807/2011-3), Fundação de Apoio à Pesquisa do Estado da Bahia (FAPESB — PNE 004/2011), Coordenação de Apoio de Pessoal de Nível Superior (CAPES) and the Graduate Program in Immunology at the Federal University of Bahia.
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SLC, RSE-B, PRB, and MFDC, planned the research and designed the experiments; PRB for drugs purification and characterization; PLCC, SRV-BF, BPSP, MNO, CSS, MSG, VDAS, and SLC performed culture-related experiments and contributed to data analysis; CSS, VDAS, RSE-B, ILON, MFDC, and SLC contributed with reagents/materials/analysis tools; PLCC, SRV-BF, BPSP, MNO, CSS, MSG, VDAS, RSE-B, and SLC for paper writing. All authors have read the final manuscript and approved the submission.
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Coelho, P.L.C., de Freitas, S.R.VB., Pitanga, B.P.S. et al. Flavonoids from the Brazilian plant Croton betulaster inhibit the growth of human glioblastoma cells and induce apoptosis. Rev. Bras. Farmacogn. 26, 34–43 (2016). https://doi.org/10.1016/j.bjp.2015.05.013
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DOI: https://doi.org/10.1016/j.bjp.2015.05.013