Anti-cancer, immunoregulatory, and antimicrobial activities of the frog skin host-defense peptides pseudhymenochirin-1Pb and pseudhymenochirin-2Pa

Milena Mechkarska, Samir Attoub, Shahrazad Sulaiman, Jelena Pantic, Miodrag L. Lukic, J. Michael Conlon

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog Pseudhymenochirus merlini (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC50<12μM) against non-small cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells but are also hemolytic against human erythrocytes (LC50=28±2μM for Ps-1Pb and LC50=6±1μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC50 against non-neoplastic human umbilical vein (HUVEC) cells=68±2μM). Ps-1Pb and Ps-2Pa (5μg/mL) significantly inhibit production of the anti-inflammatory cytokine IL-10 and the multifunctional cytokine IL-6 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages from C57BL/6 mice and enhance the production of the pro-inflammatory cytokine IL-23 from both unstimulated and LPS-stimulated macrophages. Ps-1Pb potently (MIC≤10μM) inhibits growth of multidrug-resistant clinical isolates of the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and the Gram-negative bacteria Acinetobacter baumannii and Stenotrophomonas maltophilia. Ps-2Pa shows the same high potency (MIC ≤ 10 μM) against the Gram-positive bacteria but is 2-4 fold less potent against the Gram-negative isolates. Ps-1Pb at 4 × MIC kills 99.9% of Escherichia coli within 30. min and 99.9% of S. aureus within 180 min. In conclusion, cytotoxicity against tumor cells, cytokine-mediated immunomodulatory properties, and broad-spectrum antimicrobial activity suggest that the Ps-1Pb and Ps-2Pa represent templates for design of non-hemolytic analogs for tumor therapy and for treatment of infections in cancer patients produced by multidrug-resistant pathogens.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalRegulatory Peptides
Volume194-195
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • Anti-cancer
  • Antimicrobial
  • Host-defense peptide
  • Immunoregulatory
  • Pseudhymenochirin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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