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Previous issue date: 2011-07-29 / Cancer is a term used to represent a set of more than 100 diseases, including malignant tumors from different locations. The malignancies are the second leading cause of death in the
population, representing approximately 17% of deaths of known cause. Strategies that induce differentiation have had limited success in the treatment of established cancers. In this work, a
lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated due to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death via apoptosis in tumor cells. The antiproliferative activity of CaL was tested against cell lines, with the highest inhibition of tumor growth for HeLa, reducing cell growth at a dose dependent manner, with a concentration of 10 ?g/mL. The hemolytic activity and toxicity against peripheral blood cells
were tested using the concentration of IC50 for both trials and twice the IC50 for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death
caused by CaL in HeLa cells, we performed flow cytometry and western blotting. The results showed the lectin probably induces cell death by apoptosis activation by pro-apoptotic protein
Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase, with accumulation of cells of approximately 57% in this phase, and acting as both dependent and/or independent of caspases pathway. These results suggest that CaL has the potential to be used as drug treatment against cancer. / O c?ncer ? um termo utilizado para representar um conjunto de mais de 100 patologias, incluindo tumores malignos de diferentes localiza??es. As neoplasias malignas constituem a segunda causa de morte na popula??o brasileira, representando aproximadamente 17% dos ?bitos de causa conhecida. Estrat?gias que induzem ? diferencia??o t?m tido sucesso limitado
no tratamento de c?nceres estabelecidos. Neste trabalho, uma lectina purificada da esponja marinha Cinachyrella apion (CaL) foi avaliada quanto ?s suas atividades hemol?tica, citot?xica,
antiproliferativa e quanto ? capacidade de indu??o de morte celular pela via de apoptose em c?lulas tumorais. A atividade antiproliferativa de CaL foi testada contra linhagens celulares, com maior taxa de inibi??o do crescimento para a linhagem tumoral HeLa, induzindo a inibi??o de maneira dose dependente na concentra??o de 10 ?g/mL. A atividade hemol?tica e a toxicidade contra c?lulas do sangue perif?rico foram testadas utilizando a concentra??o de IC50 para ambos os ensaios e o dobro da IC50 para a an?lise em citometria de fluxo, indicando que CaL n?o ? t?xica para estes tipos celulares. Para avaliar o mecanismo de morte celular induzida por CaL nas c?lulas HeLa, foi realizada a citometria de fluxo e western blotting. Os resultados mostraram que a lectina induz morte celular por apoptose atrav?s da ativa??o da prote?na pr?-apopt?tica
Bax, al?m de promover a parada do ciclo celular na fase S, com ac?mulo de c?lulas de aproximadamente 57% nesta fase, agindo tanto de maneira dependente como independente de caspases. Estes resultados sugerem que a CaL possui potencial para ser utilizado como f?rmaco no tratamento contra o c?ncer.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/12584 |
| Date | 29 July 2011 |
| Creators | Rabelo, Luciana Maria Ara?jo |
| Contributors | CPF:41305655400, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782221T9&dataRevisao=null, Paiva, Patr?cia Maria Guedes, CPF:36565431434, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4787593U2&dataRevisao=null, L?cio, Paulo S?rgio Marinho, CPF:49188178404, Santos, Elizeu Antunes dos |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Bioqu?mica, UFRN, BR, Bioqu?mica; Biologia Molecular |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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