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Mediators of Inflammation
Volume 2016 (2016), Article ID 2457532, 11 pages
http://dx.doi.org/10.1155/2016/2457532
Research Article

Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4

1Special Laboratory of Pain and Signaling, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil
2CEIS/Department of Biology, Institute of Biosciences of Rio Claro, São Paulo State University (UNESP), Rio Claro, SP, Brazil
3Laboratory of Pathophysiology, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil
4Department of Natural Sciences, Mathematics and Education, Agricultural Sciences Center, Federal University of São Carlos, Rodovia Anhanguera Km 174, 13600-970 Araras, SP, Brazil
5Laboratory of Inflammation and Vascular Pharmacology, Federal University of São Paulo, Rua São Nicolau 210, 09913-030 Diadema, SP, Brazil
6Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, Brazil
7Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, Brazil

Received 28 December 2015; Accepted 15 March 2016

Academic Editor: Vera L. Petricevich

Copyright © 2016 Patrícia Brigatte et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We investigated the effects of Crotoxin (CTX), the main toxin of South American rattlesnake (Crotalus durissus terrificus) venom, on Walker 256 tumor growth, the pain symptoms associated (hyperalgesia and allodynia), and participation of endogenous lipoxin A4. Treatment with CTX (s.c.), daily, for 5 days reduced tumor growth at the 5th day after injection of Walker 256 carcinoma cells into the plantar surface of adult rat hind paw. This observation was associated with inhibition of new blood vessel formation and decrease in blood vessel diameter. The treatment with CTX raised plasma concentrations of lipoxin A4 and its natural analogue 15-epi-LXA4, an effect mediated by formyl peptide receptors (FPRs). In fact, the treatment with Boc-2, an inhibitor of FPRs, abolished the increase in plasma levels of these mediators triggered by CTX. The blockage of these receptors also abolished the inhibitory action of CTX on tumor growth and blood vessel formation and the decrease in blood vessel diameter. Together, the results herein presented demonstrate that CTX increases plasma concentrations of lipoxin A4 and 15-epi-LXA4, which might inhibit both tumor growth and formation of new vessels via FPRs.