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

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...

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Main Authors: Patrícia Brigatte, Odair Jorge Faiad, Roberta Cornélio Ferreira Nocelli, Richardt G. Landgraf, Mario Sergio Palma, Yara Cury, Rui Curi, Sandra Coccuzzo Sampaio
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/2457532
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author Patrícia Brigatte
Odair Jorge Faiad
Roberta Cornélio Ferreira Nocelli
Richardt G. Landgraf
Mario Sergio Palma
Yara Cury
Rui Curi
Sandra Coccuzzo Sampaio
author_facet Patrícia Brigatte
Odair Jorge Faiad
Roberta Cornélio Ferreira Nocelli
Richardt G. Landgraf
Mario Sergio Palma
Yara Cury
Rui Curi
Sandra Coccuzzo Sampaio
author_sort Patrícia Brigatte
collection DOAJ
description 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.
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spelling doaj-art-d992efa97d2945e1b99b3343eab0cfed2025-02-03T00:59:35ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/24575322457532Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4Patrícia Brigatte0Odair Jorge Faiad1Roberta Cornélio Ferreira Nocelli2Richardt G. Landgraf3Mario Sergio Palma4Yara Cury5Rui Curi6Sandra Coccuzzo Sampaio7Special Laboratory of Pain and Signaling, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, BrazilLaboratory of Pathophysiology, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, BrazilDepartment of Natural Sciences, Mathematics and Education, Agricultural Sciences Center, Federal University of São Carlos, Rodovia Anhanguera Km 174, 13600-970 Araras, SP, BrazilLaboratory of Inflammation and Vascular Pharmacology, Federal University of São Paulo, Rua São Nicolau 210, 09913-030 Diadema, SP, BrazilCEIS/Department of Biology, Institute of Biosciences of Rio Claro, São Paulo State University (UNESP), Rio Claro, SP, BrazilSpecial Laboratory of Pain and Signaling, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, BrazilLaboratory of Pathophysiology, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, BrazilWe 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.http://dx.doi.org/10.1155/2016/2457532
spellingShingle Patrícia Brigatte
Odair Jorge Faiad
Roberta Cornélio Ferreira Nocelli
Richardt G. Landgraf
Mario Sergio Palma
Yara Cury
Rui Curi
Sandra Coccuzzo Sampaio
Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4
Mediators of Inflammation
title Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4
title_full Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4
title_fullStr Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4
title_full_unstemmed Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4
title_short Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A4
title_sort walker 256 tumor growth suppression by crotoxin involves formyl peptide receptors and lipoxin a4
url http://dx.doi.org/10.1155/2016/2457532
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