Estudo das propriedades anticâncer in vitro e in vivo do 15-Deoxigoiazensolido

• Ano de defesa: 2008
• Autor(a) principal: Pereira, Márcio Roberto Pinho
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Neoplasias; Apoptose; Lactonas
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/2750

The present study evaluated the anticancer activity of sesquiterpene lactone 15-deoxygoyazensolido. Citotoxic activity was initially evaluated by the MTT assay, where 15-deoxygoyazensolido showed IC50 < 4 μg/mL in all tested cell lines, varying from 0,09 to 0,56 μg/mL. This activity was confirmed by Trypan Blue assay, which 15-deoxygoyazensolido showed activity at 0,25, 0,5 and 1 μg/mL after 24h exposition in HL-60 cells. Afterwards, it was reveled by incorporation test of BrdU that citotoxic activity of 15-deoxygoyazensolido is related to inhibition of DNA synthesis. Besides, on the assays for induction of cellular apoptosis showed morphological alterations, DNA fragmentation, mitochondria depolarization, maintaining membrane integrity, typical apoptosis sight. The in vivo activity of 15-deoxygoyazensolido was evaluated using sarmoca 180 tumor in mice and Walker 256 tumor in rats. The sesquiterpene lactone inhibited tumor growth in a dose-dependent manner, but it was not capable to increase mice survival. The administration of 15-deoxygoyazensolido at dose 10 mg/m2/day inhibited 49,39% of solid Sarcoma 180 tumor development in transplanted mice. The histophatological assay in mice organs reveled moderate liver toxicity but these effects are considered reversible. The administration of sesquiterpene lactone inhibited Walker 256 tumor development at doses 5 e 10 mg/kg/day in transplanted rats about 34,05 e 38,80 % respectively. Concerning allergenic properties, it was not detected anti-lactone IgE antibody synthesis in swiss mice immunized with 100 μg of 15-deoxygoyazensolido. The results show that 15-deoxigoiazensolido has a potent anticancer activity, being apoptosis the mechanism of action which takes tumor cells to death.