Avaliação do efeito do alcaloide boldina sobre modelos experimentais de malignidades do sistema nervoso central e bexiga

AUTOR(ES)

Daniéli Gerhardt

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

2012

RESUMO

Plants are important sources of biologically active natural products which differ in terms of structure and biological properties. One of the biological activities of plant compounds that has attracted great interest is the ability to exert antitumoral activity in different types of cancer. Boldine is an alkaloid that occurs abundantly in the leaves and barks of boldo (Peumus boldus Mol.) a widely distributed native tree of Chile. Among other properties, boldine has been shown to exert antitumoral activity against glioma cell lines cells in vitro. Within this context, the present study was designed to evaluate the effects of boldine treatment in experimental models of gliomas and bladder cancer. Boldine was able to diminish the cell growth of C6 and U-138 MG cell lines, by inducing cell cycle arrest at G2/M phase and/or apoptosis. These findings appear to be associated to the inactivation of AKT protein and activation of GSK-3¿ protein. Additionally, the efficacy of boldine is also correlated with decrease in ERK activity. These results lead us to investigate the effect of boldine in an in vivo rat glioma experimental model. Treatment with 50 mg/Kg/day of boldine i.p. for 10 days significantly diminished the volume of implanted gliomas in rats. Additionally, pathological analysis demonstrated that malignant characteristics, such as necrosis, hemorrhage and proliferation, appeared to be lower in boldinetreated rats. Toxicological experiments with healthy rats treated with 50 mg/Kg/day of boldine i.p for 14 days did not reveal signals of tissue toxicity, gastrointestinal damage or alteration in the activity of hepatic enzymes. Moreover, the analysis of boldine effect in a model of bladder cancer in vitro, showed similar results to those observed in glioma cell lines. Boldine diminished the T24 cell growth and induced G2/M arrest and apoptosis. These findings were also related to decrease in AKT and ERK activities and increase in GSK-3¿ activity. Taken together, our results propose a novel natural compound, the alkaloid boldine, for the development of a new anticancer agent, which could be used in conjunction with the established quemotherapies regimens.

ASSUNTO(S)

ensaios de seleção de medicamentos antitumorais neoplasias da bexiga urinária glioma plantas medicinais

Documentos Relacionados

• Investigação do efeito do alcalóide boldina sobre a proliferação de linhagens de glioma humano e de rato
• Avaliação do sistema nervoso central do feto e neonato
• Modulação da via da Akt por desidroepiandrosterona (DHEA) no sistema nervoso central de ratos em diferentes modelos experimentais
• Investigação do efeito neuroprotetor do alcalóide boldina sobre a morte celular induzida pela privação de oxigênio e glicose em culturas organotípicas de hipocampo de rato
• Efeito promnésico e antioxidante do café no sistema nervoso central de ratos