Interactions of PLA2-s from Vipera lebetina, Vipera berus berus and Naja naja oxiana venom with platelets, bacterial and cancer cells.
Secretory phospholipasesA(2) (sPLA(2)s) form a large family of structurally related enzymes widespread in nature. Herein, we studied the inhibitory effects of sPLA(2)s from Vipera lebetina (VLPLA(2)), Vipera berus berus (VBBPLA(2)), and Naja naja oxiana (NNOPLA(2)) venoms on (i) human platelets, (ii) four different bacterial strains  (gram-negative Escherichia coli and Vibrio fischeri; gram-positive Staphylococcus aureus and Bacillus subtilis) and (iii) five types of cancer cells (PC-3, LNCaP, MCF-7, K-562  and B16-F10) in vitro. sPLA(2)s inhibited collagen-induced platelet aggregation:  VBBPLA(2) IC(50) = 0.054, VLPLA(2) IC(50) = 0.072, NNOPLA(2) IC(50) = 0.814 μM.  p-Bromophenacylbromide-inhibited sPLA(2) had no inhibitory action on platelets. 36.17 μM VBBPLA(2 )completely inhibited the growth of gram-positive Bacillus subtilis whereas no growth inhibition was observed towards gram-negative Escherichia coli. The inhibitory action of sPLA(2)s (~0.7 μM and ~7 μM) towards cancer cells depended on both venom and cell type. VBBPLA(2 )(7.2 μM) inhibited significantly the viability of K-562 cells and the cell death appeared apoptotic. The sPLA(2)s exhibited no inhibitory effect towards LNCaP cells and some effect (8%-20%) towards other cells. Thus, already sub-μM concentrations of sPLA(2)s inhibited collagen-induced platelet aggregation and from the current suite of studied svPLA(2)s and test cells, VBBPLA(2) was the most growth inhibitory towards  Bacillus subtilis and K-562 cells.
National Institute of Chemical Physics and Biophysics, Tallinn, Estonia. mari.samel@kbfi.ee
Mari
M
Samel
Heiki
H
Vija
Imbi
I
Kurvet
Kai
K
Künnis-Beres
Katrin
K
Trummal
Juhan
J
Subbi
Anne
A
Kahru
Jüri
J
Siigur
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004546:Elapid Venoms / Q000201:enzymology*; D017815:Elapidae; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D054467:Phospholipases A2 / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D016415:Sequence Alignment; D014757:Viper Venoms / Q000201:enzymology*; D017819:Viperidae
D000900:Anti-Bacterial Agents; D003603:Cytotoxins; D004546:Elapid Venoms; D014757:Viper Venoms; D054467:Phospholipases A2