Cytotoxic peptides with insulin-releasing activities from skin secretions of the Italian stream frog Rana italica (Ranidae)

J Pept Sci. 2017 Oct;23(10):769-776. doi: 10.1002/psc.3025. Epub 2017 Jul 11.

Abstract

Peptidomic analysis of norepinephrine-stimulated skin secretions from Italian stream frog Rana italica led to the purification and characterization of two host-defense peptides differing by a single amino acid residue belonging to the brevinin-1 family (brevinin-1ITa and -1ITb), a peptide belonging to the temporin family (temporin-ITa) and a component identified as prokineticin Bv8. The secretions contained relatively high concentrations of the methionine-sulphoxide forms of brevinin-1ITa and -1ITb suggesting that these peptides may have a role as antioxidants in the skin of this montane frog. Brevinin-1ITa (IVPFLLGMVPKLVCLITKKC) displayed potent cytotoxicity against non-small cell lung adenocarcinoma A549 cells (LC50 = 18 μM), breast adenocarcinoma MDA-MB-231 cells (LC50 = 8 μM) and colorectal adenocarcinoma HT-29 cells (LC50 = 18 μM), but the peptide was also strongly hemolytic against mouse erythrocytes (LC50 = 7 μM). Temporin-ITa (VFLGAIAQALTSLLGKL.NH2 ) was between three and fivefold less potent against these cells. Brevinin-1ITa inhibited growth of both Gram-positive Staphylococcus epidermidis and Gram-negative Escherichia coli as well as a strain of the opportunist yeast pathogen Candida parapsilosis, whereas temporin-ITa was active only against S. epidermidis and C. parapsilosis. Both peptides stimulated the release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥1 nM, but brevinin-1ITa was cytotoxic to the cells at concentrations ≥3 μM. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Keywords: Ranidae; antimicrobial peptide; cytotoxicity; frog skin; insulin release.

MeSH terms

  • Amphibian Proteins / metabolism*
  • Amphibian Proteins / pharmacology
  • Amphibian Proteins / toxicity
  • Animals
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Cationic Peptides / toxicity
  • Anura / metabolism
  • Escherichia coli / drug effects
  • HT29 Cells
  • Hemolysis / drug effects
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Ranidae
  • Skin / metabolism*
  • Staphylococcus epidermidis / drug effects

Substances

  • Amphibian Proteins
  • Antimicrobial Cationic Peptides