title: Peptides with in vitro anti-tumor activity from the venom of the Eastern green mamba, Dendroaspis angusticeps (Elapidae).
abstract: 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).
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Manju
authors.initials: M
authors.lastname: Prajeep
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Milena
authors.initials: M
authors.lastname: Mechkarska
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Kholoud
authors.initials: K
authors.lastname: Arafat
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Abdu
authors.initials: A
authors.lastname: Adem
authors.affiliation: Laboratorio de Venómica Estructural y Funcional, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
authors.forename: Davinia
authors.initials: D
authors.lastname: Pla
authors.affiliation: Laboratorio de Venómica Estructural y Funcional, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
keywords: Dendroaspis; anti-cancer activity; cytotoxicity; toxin C13S1C1; toxin F-VIII