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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer

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Autor(es):
Costa, Tassia R. ; Menaldo, Danilo L. ; Zoccal, Karina F. ; Burin, Sandra M. ; Aissa, Alexandre F. ; de Castro, Fabiola A. ; Faccioli, Lucia H. ; Greggi Antunes, Lusania M. ; Sampaio, Suely V.
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 7, FEB 16 2017.
Citações Web of Science: 17
Resumo

L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced in vivo and in vitro by CR-LAAO, an L-amino acid oxidase isolated from Calloselasma rhodostoma venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses in vivo, with recruitment of neutrophils and release of IL-6, IL-1 beta, LTB4 and PGE(2). In vitro, IL-6 and IL-1 beta production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4. In addition, CR-LAAO promoted apoptosis of HL-60 and HepG2 tumor cells mediated by the release of hydrogen peroxide and activation of immune cells, resulting in oxidative stress and production of IL-6 and IL-1 beta that triggered a series of events, such as activation of caspase 8, 9 and 3, and the expression of the pro-apoptotic gene BAX. We also observed that CR-LAAO modulated the cell cycle of these tumor cells, promoting delay in the G0/G1 and S phases. Taken together, our results suggest that CR-LAAO could serve as a potential tool for the development of novel immunotherapeutic strategies against cancer, since this toxin promoted apoptosis of tumor cells and also activated immune cells against them. (AU)

Processo FAPESP: 15/00740-0 - Avaliação do potencial terapêutico de L-aminoácido oxidases isoladas de peçonhas de serpentes como antitumoral: estudos de genotoxicidade e expressão gênica
Beneficiário:Tássia Rafaella Costa
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
Beneficiário:Suely Vilela
Linha de fomento: Auxílio à Pesquisa - Temático