Avaliação do potencial citotóxico, do perfil de morte celular in vitro e da atividade antitumoral in vivo induzidos pela resina floral e látex dos frutos de Clusia sp.

• Autor(a) principal: Santos , Alexandre Pereira dos
• Data de Publicação: 2013
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/6851
• topic: Clusia; Câncer; Apoptose; K562; Câncer; Clusia; Apoptosis; K562; CIENCIAS DA SAUDE

For many centuries the plants are supplied raw material to produce an armory of therapeutic agents, either by synthesis or from metabolites of their own use. In this context especially species of the Cerrado region. A new species of Clusia still unidentified (Clusia sp) in endemic regions of Goiânia and Chapada dos Veadeiros has been popularly employed as antirheumatic agent, purgative, febrifuge, stomach problems as described for other species of the genus, and its application as anticancer agent . The number of studies confirming the application of this kind for cancer treatment is scarce justifying this work. we evaluated the potential antileucêmico in vitro and in vivo antitumor floral resin and latex obtained from the fruits of Clusia sp. Investigated and elucidated the possible mechanisms of action of these products on cell death and toxicity. Cytotoxicity screening performed on these samples K562, Lucena, HL-60, B16F10, PC3 and lymphocytes. Analyzed cell morphology after treatment of K562 cells with the resin and latex; evaluated the increased survival of animals after treatment with plant samples, estimated acute oral toxicity of resin and latex Clusia sp from cells of basal metabolism 3T3, investigated the potential hemolytic and immunosuppressive these vegetables samples. The results obtained from the tests carried out show interesting cytotoxic action in leukemia cells with IC50 values at 24, 48 and 72 hours resin 62,2, 31,1 and 5,09 µg/ml for the latex and 37,4; 14,5, and 8,58 µg/mL, respectively. Compared with the drugs used in therapy, such as Imatinib was not statistically significant difference between latex and imatinib mesylate, a drug used as reference in the treatment of leukemia. From the tests morphology with Giemsa or Hoechst was observed that both samples vegetables induced morphological changes typical of cell death in apoptosis. After treatment with the resin (62,2 µg/mL) and latex (37,4 µg/mL) was observed chromatin condensation, DNA fragmentation from the formation of apoptotic bodies, among other events that attest to cell death. In an attempt to elucidate the mechanism of death by flow cytometry was observed after treatment with the the resin and latex, externalization of phosphatidylserine, inducing the formation of reactive oxygen species, activation of caspases -3, -8 and -9, reducing mitochondrial membrane potential, release of cytochrome c, activation of Bax, all these processes involved in cell death. Increased survival in tumor-bearing animals were observed at doses of 125 mg/kg of resin and 250 mg/kg latex, higher doses were toxic. From the results of the estimated DL50 vegetable samples were classified in category 3 of the GHS. Immunosuppressive effect was observed for the resin and latex and moderate hemolytic was observed only for the resin. Given the above samples resin and latex Clusia sp exhibit interesting profile for the development of anticancer drugs.