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Doctoral Thesis
DOI
https://doi.org/10.11606/T.85.2012.tde-24082012-133252
Document
Author
Full name
Rodrigo Guimaraes Queiroz
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Nascimento, Nanci do (President)
Affonso, Regina
Alves, Janaina Baptista
Pimenta, Daniel Carvalho
Vieira, Daniel Perez
Title in Portuguese
Componentes derivados de venenos de serpentes com ação antitumoral em células de melanoma Murino
Keywords in Portuguese
atividade antitumoral
melanoma
toxinas
venenos de serpentes
Abstract in Portuguese
Apesar dos constantes avanços no tratamento de câncer, essa doença continua sendo umas das principais causas de mortalidade no mundo todo, portanto, é imperativo que novas modalidades de tratamento sejam desenvolvidas. Venenos de serpentes causam uma variedade de efeitos biológicos, pois constituem uma mistura complexa de substâncias como disintegrinas, proteases (serino e metalo), fosfolipases A2, L-aminoácido oxidases entre outras. No presente trabalho pesquisou-se em alguns venenos de serpentes frações com atividade antitumoral, pois há relatos de compostos ofídicos que apresentam esta atividade. Após fracionamento de venenos de serpentes das famílias Viperidae e Elapidae foram feitas incubações das frações obtidas com células normais de fibroblasto L929 e de melanoma B16-F10. Os resultados mostraram que as frações do veneno da serpente Notechis ater niger apresentaram a maior especificidade e potencial antitumoral em células de melanoma murino B16-F10 que os demais venenos utilizados. Este achado, aliado ao fato de ser um veneno pouco explorado foram determinantes para que este veneno fosse selecionado para dar continuidade aos estudos. As frações citotóxicas deste veneno foram submetidas a análises para identificar e caracterizar os componentes que apresentaram esta atividade atitumoral. Ensaios de western-blot e zimografia sugerem que estas proteínas não pertencem à classe das metalo e serinoproteinases.
Title in English
Snake venoms components with antitumor activity in murine melanoma cells
Keywords in English
anti-tumoral activity
melanoma
snake venom
toxins
Abstract in English
Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases.
 
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Publishing Date
2012-11-09
 
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