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

5 years ago

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

Laurent Coquet, Maria Luisa Mangoni, Yasser H. A. Abdel-Wahab, Andrea C. Rinaldi, Thierry Jouenne, Jérôme Leprince, J. Michael Conlon, Peter R. Flatt, Vishal Musale, Samir Attoub

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. Peptidomic analysis of secretions from the Italian stream frog Rana italica led to the purification and characterization of brevinin 1ITa and 1ITb together with their methionine-sulfoxide forms, temporin ITa and prokineticin Bv8. Brevinin 1ITa displayed potent cytotoxicity against a range of tumor cell lines and broad-spectrum antimicrobial activity but was strongly hemolytic. Both brevinin 1ITa and temporin ITa 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/psc.3025