In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines

Peptides. 2003 Jul;24(7):945-53. doi: 10.1016/s0196-9781(03)00194-3.


In order to develop peptide agents with reduced length and enhanced tumoricidal activity, we have designed gaegurin 6 (GGN6) derivatives through deletions and/or substitutions of amino acids. The deletion of hydrophobic amino terminal region completely abolished antitumor activity whereas the deletion of carboxy terminal region had little influence on antitumor activity. Antitumor activity of the PTP peptides did not correlate with antibacterial activity. PTP7, the most potent derivative, was found to have comparable antitumor activity to GGN6 in spite of reduced number of amino acids which is about half the size of gaegurin 6; furthermore, it showed little cytotoxicity on PBMCs and RBCs. GGN6 and PTP7 also showed equivalent cytotoxicity against drug sensitive (MCF-7) and multidrug-resistant cell lines (MCF-7/DOX). Plasma membrane blebbing and DNA fragmentation of peptide-treated tumor cells indicated that the peptides could induce apoptosis in tumor cells. These results suggest that GGN6 and its derivatives can be developed as new anticancer agents and may provide a new strategy for overcoming MDR which is a major problem in cancer therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Drug Design
  • Drug Resistance, Multiple / physiology
  • Drug Resistance, Neoplasm*
  • Drug Screening Assays, Antitumor
  • Erythrocytes / drug effects
  • Escherichia coli / drug effects
  • Hemolysis / drug effects
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • Klebsiella pneumoniae / drug effects
  • Leukocytes, Mononuclear / drug effects
  • Microbial Sensitivity Tests
  • Microscopy
  • Molecular Sequence Data
  • Paclitaxel / pharmacology
  • Peptides / chemical synthesis
  • Peptides / pharmacology
  • Protein Precursors / chemical synthesis
  • Protein Precursors / chemistry
  • Protein Precursors / pharmacology*
  • Salmonella typhimurium / drug effects


  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Peptides
  • Protein Precursors
  • gaegurin 6
  • Doxorubicin
  • Paclitaxel