Antitumor and angiostatic peptides from frog skin secretions

Abstract

The discovery of new molecules with potential antitumor activity continues to be of great importance in cancer research. In this respect, natural antimicrobial peptides isolated from various animal species including humans and amphibians have been found to be of particular interest. Here, we report the presence of two anti-proliferative peptides active against cancer cells in the skin secretions of the South American tree frog, Phyllomedusa bicolor. The crude skin exudate was fractioned by size exclusion gel followed by reverse-phase HPLC chromatography. After these two purification steps, we identified two fractions that exhibited anti-proliferative activity. Sequence analysis indicated that this activity was due to two antimicrobial α-helical cationic peptides of the dermaseptin family (dermaseptins B2 and B3). This result was confirmed using synthetic dermaseptins. When tested in vitro, synthetic B2 and B3 dermaseptins inhibited the proliferation of the human prostatic adenocarcinoma PC-3 cell line by more than 90%, with an EC50 of around 2–3 μM. No effect was observed on the growth of the NIH-3T3 non-tumor mouse cell line with Drs B2, whereas a slight inhibiting effect was observed with Drs B3 at high dose. In addition, the two fractions obtained after size exclusion chromatography also inhibited PC-3 cell colony formation in soft agar. Interestingly, inhibition of the proliferation and differentiation of activated adult bovine aortic endothelial cells was observed in cells treated with these two fractions. Dermaseptins B2 and B3 could, therefore, represent interesting new pharmacological molecules with antitumor and angiostatic properties for the development of a new class of anticancer drugs.

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Acknowledgments

Hanneke van Zoggel was funded by a Grant from the French Agence Nationale de la Recherche (ANR-06-RIB 016-02) and by the French Association pour la Recherche sur le Cancer. Cécile Galanth was funded by the French Ministère délégué à l’enseignement supérieur et à la recherche. This work was partly supported by a Grant from ANR (ANR-06-RIB 016-02) and a Grant from the French Institut national du cancer (INCA-PL06-093) from the Centre National de la Recherche Scientifique. We thank Dr. C. Piesse (Plate-forme Ingénierie des Protéines et Synthèse Peptidique, IFR 83, Université Pierre et Marie Curie, Paris, France) for the synthesis and purification of peptides.

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Correspondence to Jean Delbé.

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van Zoggel, H., Hamma-Kourbali, Y., Galanth, C. et al. Antitumor and angiostatic peptides from frog skin secretions. Amino Acids 42, 385–395 (2012). https://doi.org/10.1007/s00726-010-0815-9

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Keywords

  • Antimicrobial peptide
  • Dermaseptin
  • Antitumor activity
  • Angiogenesis