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

Patrícia Brigatte,Mario Sergio Palma,Richardt G Landgraf,Rui Curi,Yara Cury,Roberta Cornélio Ferreira Nocelli,Sandra Coccuzzo Sampaio,Odair Jorge Faiad

doi:10.1155/2016/2457532

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.

Highlights

Crotoxin (CTX) is the main toxic component of the venom of the South American rattlesnake, Crotalus durissus terrificus [1, 2]
CTX Inhibited the Edema Induced by Inoculation of Walker 256 Carcinoma Cells in the Plantar Region of the Rat Right Hind Paw, Decreased Formation of New Blood Vessels, and the Blood Vessel Diameters
Tumor growth induced by intraplantar inoculation of Walker 256 carcinoma cells in rats was assessed by the increase in volume of the glabrous region of the hind paw

Summary

Introduction

Crotoxin (CTX) is the main toxic component of the venom of the South American rattlesnake, Crotalus durissus terrificus [1, 2]. Several studies have shown antitumor effects of snake venoms or their isolated components [3,4,5,6,7,8,9]. CTX has been shown to inhibit proliferation of various cell lines (in vitro) and growth of various tumors in vivo [10]. As reported by Cura and colleagues [11], CTX is toxic to several tumor cell lines in vitro [7] and, in some of them, via epidermal growth factor receptors [12]. The antitumoral effects of CTX have been reported in patients with lung and mammary carcinoma [8]. Evidence has been accumulated that CTX presents inhibitory effects on inflammatory response [13, Mediators of Inflammation

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Results

Conclusion