Peptides with in vitro anti-tumor activity from the venom of the Eastern green mamba, Dendroaspis angusticeps (Elapidae)
J Venom Res (2014), Vol 5, 16-21
Published online: 19 June 2014
J Michael Conlon α,*, Manju Prajeep α, Milena Mechkarska α,Kholoud Arafat β, Samir Attoub β, Abdu Adem β, Davinia Pla §, Juan J Calvete §
α Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
β Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
§ Laboratorio de Venómica Estructural y Funcional, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain
*Correspondence to: J Michael Conlon, E-mail: firstname.lastname@example.org, Tel: +791 3 7137484, Fax: +791 3 7672033
Received: 22 April 2014; Revised: 19 June 2014; Accepted: 19 June 2014
© Copyright The Author(s). First Published by Library Publishing Media. This is an open access article, published under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0). This license permits non-commercial use, distribution and reproduction of the article, provided the original work is appropriately acknowledged with correct citation details.
Two structurally related (48.6% amino acid sequence identity) peptides with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells were purified from the venom of the Eastern green mamba Dendroaspis angusticeps using reversed phase HPLC. The peptides were identified as members of the three-finger superfamily of snake toxins by mass fingerprinting of tryptic digests. The more potent peptide (LC50 against A549 cells = 56±4µg/ml) was identical to the previously described toxin C13S1C1 and the less active peptide (LC50 against A549 cells = 106±5µg/ml) was identical to toxin F-VIII. Toxin C13S1C1 was also cytotoxic against breast adenocarcinoma MDA-MB-231 cells (LC50 = 62±2µg/ml) and colorectal adenocarcinoma HT-29 cells (LC50 = 110±4µg/ml). Although the peptide was appreciably less hemolytic activity against human erythrocytes (LC50 >600µg/ml), it was cytotoxic to human umbilical vein endothelial HUVEC cells (57±3µg/ml) indicating no differential activity against cell lines derived from neoplastic tissues. Toxin F-VIII was not cytotoxic to MDA-MB-231, HT-29 cells, and HUVEC cells at concentrations up to 300µg/ml and was not hemolytic at concentrations up to 1mg/ml. Neither peptide inhibited growth of reference strains of Escherichia coli or Staphylococcus aureus (MIC values >200μg/ml).
KEYWORDS: Dendroaspis, cytotoxicity, anti-cancer activity, toxin C13S1C1, toxin F-VIII