Propriedades anticâncer de pterocarpanos naturais

• Autor(a) principal: Militão, Gardênia Carmen Gadelha
• Data de Publicação: 2007
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/62477
• topic: Ensaios de Seleção de Medicamentos Antitumorais; Leguminosa; Antineoplásicos; Pterocarpanos

Pterocarpans are compounds with a tetracyclic ring system derived from the basic isoflavonoid skeleton. The purpose of this study was to evaluatc the antitumor activity of pterocarpans and investigate the mode of pharmacological action of these compounds. The compound 2,3,9-trimethoxypterocarpan showed cytotoxic activity against all tumor cell lines tested. Only L929, a normal cell line, was not affected (IC50 > 25 pg/mL). Pcripheral blood mononucleated cells (PMBC) also seemed to be resistant to 2,3,9-trimethoxypterocarpan.. The cytotoxicity of the two trimethoxylated pterocarpan derivatives, 3,9,10- trimethoxypterocarpan e 3,4,9-trimethoxypterocarpan, was also evaluated and neither of these reduced tumor cell count. In order to understand the mode of action of these pterocarpans, MCF-7 cytoskeleton was studied using immunofluorescence. After 24 hours, treated cells were arrested at prometaphase. Some of these cells presented a monoastcr spindle while other presented a multiaster spindle. No morphological alterations in interphasic microtubules nor actin was observed after treatment with 2,3,9-trimethoxypterocarpan. The measurement of cellular DNA content using flow cytometry indicated that 2,3,9-trimethoxypterocarpan caused cell cycle arrest at G2/M after 24 h incubation. Most of the arrested cells re-entered cell cycle ♦ after an additional 24h-period of incubation in a drug-free médium, indicating that the effect is reversible. However, after 48h treatment, the subdiploid DNA content increased and morphological analysis revealed the presence of multinucleated cells.