Antitumor and angiostatic activities of the antimicrobial peptide dermaseptin B2

PLoS One. 2012;7(9):e44351. doi: 10.1371/journal.pone.0044351. Epub 2012 Sep 20.

Abstract

Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphibian Proteins / pharmacology*
  • Animals
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Nude
  • Microscopy, Confocal
  • Xenograft Model Antitumor Assays

Substances

  • Amphibian Proteins
  • Antimicrobial Cationic Peptides
  • Antineoplastic Agents
  • dermaseptin B2, Phyllomedusa bicolor
  • L-Lactate Dehydrogenase
  • Caspase 3

Grant support

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. 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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.