Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)

Conlon, JM, Attoub, S, Musale, V, Leprince, J, Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719, Sanz, L and Calvete, JJ (2020) 'Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)'. Toxicon, Vol 6, e100030.

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Abstract

Four peptides with cytotoxic activity against BRIN-BD11 rat clonal β-cells were purified from the venom of the black-necked spitting cobra Naja nigricollis using reversed-phase HPLC. The peptides were identified as members of the three-finger superfamily of snake toxins by ESI-MS/MS sequencing of tryptic peptides. The most potent peptide (cytotoxin-1N) showed strong cytotoxic activity against three human tumour-derived cell lines (LC50 = 0.8 ± 0. 2 µM for A549 non-small cell lung adenocarcinoma cells; LC50 = 7 ± 1 µM for MDA-MB-231 breast adenocarcinoma cells; and LC50 = 9 ± 1 µM for HT-29 colorectal adenocarcinoma cells). However, all the peptides were to varying degrees cytotoxic against HUVEC human umbilical vein endothelial cells (LC50 in the range 2-22 µM) and cytotoxin-2N was moderately hemolytic (LC50 = 45 ± 3 µM against mouse erythrocytes). The lack of differential activity against cells derived from non-neoplastic tissue limits their potential for development into anti-cancer agents. In addition, two proteins in the venom, identified as isoforms of phospholipase A2, effectively stimulated insulin release from BRIN-BD11 cells (an approximately 6-fold increase in rate compared with 5.6 mM glucose alone) at a concentration (1 µM) that was not cytotoxic to the cells suggesting possible application in therapy for Type 2 diabetes.

Item Type:	Article
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 68 Peptides QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins QY Clinical Pathology > QY 25 Laboratory techniques and procedure WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.toxcx.2020.100030
Depositing User:	Mary Creegan
Date Deposited:	03 Apr 2020 18:14
Last Modified:	09 Apr 2020 10:02
URI:	https://archive.lstmed.ac.uk/id/eprint/13943

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