Cytotoxic and peptidase inhibitory activities of selected non-hepatotoxic cyclic peptides from cyanobacteria.
Toxic cyanobacterial blooms are a rich source of metabolites having a variety of biological activities. Two main groups of cyclic peptides, depsipeptides and ureido linkage-containing peptides, reportedly inhibit serine peptidases. We characterised their inhibitory properties against selected peptidases and investigated their influence on cell viability. The depsipeptide planktopeptin BL1125 is a strong linear competitive tight-binding inhibitor of leukocyte (K(i)=2.9 nm) and pancreatic (K(i)=7.2 nm) elastase and also of chymotrypsin (K(i)=6.1 nm). Anabaenopeptins B and F show no inhibition against chymotrypsin, but inhibit both elastases. The tested cyclic peptides do not inhibit trypsin, urokinase, kallikrein 1 or cysteine peptidases. All three tested cyanopeptides show no short-term cytotoxicity in concentrations of up to 10 mum, but impair the metabolic activity of normal human astrocytes after prolonged exposure (48-96 h), whereas glioblastoma cells, tumour cells of the same type, are resistant. Strong inhibition and relative selectivity of the tested cyanopeptides suggests that they are potential candidates for application in inflammatory diseases and possibly some types of cancers.
Bubik
Anja
A
Department of Genetic Toxicology, National Institute of Biology, Vecna pot 111, POB 141, SI-1001 Ljubljana, Slovenia.
Sedmak
Bojan
B
Novinec
Marko
M
Lenarcic
Brigita
B
Lah
Tamara T
TT
D001253:Astrocytes / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D000458:Cyanobacteria / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects; D010447:Peptide Hydrolases / Q000009:adverse effects*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D003603:Cytotoxins; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D010447:Peptide Hydrolases