Novel antimicrobial peptides with high anticancer activity and selectivity

PLoS One. 2015 May 13;10(5):e0126390. doi: 10.1371/journal.pone.0126390. eCollection 2015.

Abstract

We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antibiotics, Antineoplastic / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Escherichia coli / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • Antimicrobial Cationic Peptides

Grants and funding

This work is supported by grants from the Minister of Science and Technology, Taiwan. B.S. Yip is supported by research grants from National Taiwan University Hospital.