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Neoplasia ; 7(6): 563-74, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16036107

RESUMO

In this work, we investigated the effects of Casiopeina II-gly (Cas IIgly)--a new copper compound exhibiting antineoplastic activity--on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas IIgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS) formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas IIgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF) and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-L-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas IIgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas IIgly. ROS formation induced by Cas IIgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas IIgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas IIgly for the treatment of malignant gliomas.


Assuntos
Caspases/metabolismo , Cobre/farmacologia , Glioma/tratamento farmacológico , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Acetilcisteína/farmacologia , Transporte Ativo do Núcleo Celular , Animais , Antioxidantes/farmacologia , Apoptose , Western Blotting , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Cromatina/metabolismo , Fragmentação do DNA , Relação Dose-Resposta a Droga , Técnicas In Vitro , Peroxidação de Lipídeos , Potenciais da Membrana , Mitocôndrias/patologia , Nucleossomos/metabolismo , Transporte Proteico , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Frações Subcelulares
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