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Arazyme, a proteolytic enzyme, as a new anti-tumor therapeutic approach

Grant number: 07/00124-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2007
Effective date (End): December 31, 2007
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Elaine Guadelupe Rodrigues
Grantee:Felipe Valença Pereira
Home Institution: Departamento de Microbiologia, Imunologia e Parasitologia. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

New therapeutic approaches are actively searched for cancer treatment because of the side effects induced by available chemotherapeutic drugs. Several possibilities are under study, and the use of exogenous proteases, isolated from bacteria, plants or even animals, is one of them. In fact, these molecules are being already used in several pathologies. Plant proteases, like trypsin, brofazyn, papain, chimotrypsin and others, are being experimentally used for cancer treatment. They inhibited in vitro tumor growth, and in vivo invasion and metastasis on treated animals, however, their mechanism of action is not described yet. Arazyme, a metalloprotease belonging to Serralysin family and isolated from Serratia proteamaculans culture supernatant, a symbiotic bacterium of the spider Nephila clavata, in previous assays in our lab inhibited in vitro growth of murine and human tumor cell lines, stimulated peritoneal macrophages to secrete nitric oxide, and preliminary results suggest that this protease has an anti-metastatic activity in vivo. The objective of this project is to continue these studies in order to analyze the usefulness of Arazyme as a new therapeutic agent against B16F10-Nex2 murine melanoma, determining the importance of the enzymatic activity for this effect, and also determining the mechanism of in vitro and in vivo antitumor activity. (AU)