Open AccessFlavonoids from the Brazilian plant Croton betulaster inhibit the growth of human glioblastoma cells and induce apoptosis
Author(s) -
Paulo Lucas Cerqueira Coelho,
Sandra Freitas,
Bruno Penas Seara Pitanga,
Víctor Diógenes Amaral da Silva,
Mo. Oliveira,
Maria Socorro Grangeiro,
Catiane Souza,
Ramon dos Santos El-Bachá,
Maria de Fátima Dias Costa,
Pedro Barbosa,
Ivascimento,
Sílvia Lima Costa
Publication year - 2016
Publication title -
revista brasileira de farmacognosia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 46
eISSN - 1981-528X
pISSN - 0102-695X
DOI - 10.1016/j.bjp.2015.05.013
Subject(s) - apoptosis , fragmentation (computing) , cell growth , chemistry , croton , cell culture , viability assay , biochemistry , pharmacology , biology , ecology , genetics , organic chemistry
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