Anti-tumor activity of an antibiotic peptide derived from apoprotein E

In Vivo. 2005 Jan-Feb;19(1):261-4.

Abstract

Background: Recently, we found that a 30-mer peptide derived from apoprotein E (apoE) 133-162 has antibiotic activity that is comparable with the classic antibiotics and neutrophil-derived antibiotic peptide. In this study, we tested if apoE 133-162 also has anti-tumor activity against several cancer cell lines.

Materials and methods: Two gastric cancer cell lines (MKN-7, MNN-1), two pancreatic cancer cell lines (PANC-1, Paca-2) and one colon cancer cell line (COLO201) were used for MTT cytotoxic assay. Calcein leakage from artificial liposomes was also tested, varying the composition of liposome.

Results: The apoE 133-162 peptide had cytotoxic activity against all tested human cancer cell lines in a dose-dependent manner. In the Paca-2 cell, an equivalent cytotoxic activity to 5-FU (10 microg/ml) was observed at about 40 microg/ml of apoE 133-162 peptide, but no synergistic effect of apoE 133-162 (40 microg/ml ) with 5-FU (10 microg/ml), nor inhibitory effect by heparin(100 microg/ml), was observed. In the calcein leakage test, in the presence of 150 mM NaCl, the presence of cholesterol attenuated the membrane perturbation activity of apoE 133-162, and the more acidic membrane was susceptible to lysis.

Conclusion: ApoE 133-162 has anti-tumor activity, probably through perturbation and formation of ion-permeable "pores" in membranes.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apolipoproteins E / chemistry*
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Growth Inhibitors / pharmacology*
  • Humans
  • Neoplasms / drug therapy*
  • Pancreatic Neoplasms / drug therapy
  • Peptides*
  • Stomach Neoplasms / drug therapy

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Apolipoproteins E
  • Growth Inhibitors
  • Peptides