title: Walker 256 Tumor Growth Suppression by Crotoxin Involves Formyl Peptide Receptors and Lipoxin A₄.
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.
authors.affiliation: Special Laboratory of Pain and Signaling, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil; CEIS/Department of Biology, Institute of Biosciences of Rio Claro, São Paulo State University (UNESP), Rio Claro, SP, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Brigatte
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil.
authors.forename: Odair Jorge
authors.initials: OJ
authors.lastname: Faiad
authors.affiliation: Department of Natural Sciences, Mathematics and Education, Agricultural Sciences Center, Federal University of São Carlos, Rodovia Anhanguera Km 174, 13600-970 Araras, SP, Brazil.
authors.forename: Roberta Cornélio
authors.initials: RC
authors.lastname: Ferreira Nocelli
authors.affiliation: Laboratory of Inflammation and Vascular Pharmacology, Federal University of São Paulo, Rua São Nicolau 210, 09913-030 Diadema, SP, Brazil.
authors.forename: Richardt G
authors.initials: RG
authors.lastname: Landgraf
authors.affiliation: CEIS/Department of Biology, Institute of Biosciences of Rio Claro, São Paulo State University (UNESP), Rio Claro, SP, Brazil.
authors.forename: Mario Sergio
authors.initials: MS
authors.lastname: Palma
authors.affiliation: Special Laboratory of Pain and Signaling, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil.
authors.forename: Yara
authors.initials: Y
authors.lastname: Cury
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, Brazil.
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, Avenida Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 1524, 05508-900 São Paulo, SP, Brazil.
authors.forename: Sandra Coccuzzo
authors.initials: SC
authors.lastname: Sampaio
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003439:Crotoxin / Q000627:therapeutic use*; D044045:Lipoxins / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044042:Receptors, Formyl Peptide / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; C040527:lipoxin A4; D003439:Crotoxin