title: Cytotoxic activities of [Ser⁴⁹]phospholipase A₂ from the venom of the saw-scaled vipers Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus.
abstract: Fractionation by reversed-phase HPLC of venom from four species of saw-scaled viper: Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus led to identification in each sample of an abundant protein with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. The active component in each case was identified by MALDI-TOF mass fingerprinting of tryptic digests as [Ser⁴⁹]phospholipase A₂ ([Ser⁴⁹]PLA₂). An isoform of [Ser⁴⁹]PLA₂ containing the single Ala¹⁸→ Val substitution and a partially characterized [Asp⁴⁹]PLA₂ were also present in the E. coloratus venom. LC₅₀ values against A549 cells for the purified [Ser⁴⁹]PLA₂ proteins from the four species are in the range 2.9-8.5 μM. This range is not significantly different from the range of LC₅₀ values against human umbilical vein endothelial HUVEC cells (2.5-12.2 μM) indicating that the [Ser⁴⁹]PLA₂ proteins show no differential anti-tumor activity. The LC₅₀ value for [Ser⁴⁹]PLA₂ from E. ocellatus against human erythrocytes is >100 μM and the MIC values against Escherichia coli and Staphylococcus aureus are >100 μM. It is suggested that the [Ser⁴⁹]PLA₂ proteins play a major role in producing local tissue necrosis and hemorrhage at the site of envenomation.
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, United Arab Emirates. jmconlon@uaeu.ac.ae
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.forename: Hama
authors.initials: H
authors.lastname: Arafat
authors.forename: Milena
authors.initials: M
authors.lastname: Mechkarska
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Casewell
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrison
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D054467:Phospholipases A2 / Q000302:isolation & purification / Q000494:pharmacology*; D012909:Snake Bites / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D014757:Viper Venoms / Q000494:pharmacology*; D017819:Viperidae / Q000145:classification
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D014757:Viper Venoms; D054467:Phospholipases A2
keywords: Adenocarcinoma A549 cells; Anti-cancer activity; Cytotoxicity; Echis; Human umbilical vein endothelial cells; Phospholipase A(2)