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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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Author(s):
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.
Total Authors: 9
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, FEB 16 2017.
Web of Science Citations: 17
Abstract

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)

FAPESP's process: 15/00740-0 - Therapeutic potential evaluation of L-amino acid oxidases isolated from snake venoms as antitumor: genotoxicity and gene expression studies
Grantee:Tássia Rafaella Costa
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
Grantee:Suely Vilela
Support type: Research Projects - Thematic Grants