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


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.


CONCLUSIONS
ApoE 133-162 has anti-tumor activity, probably through perturbation and formation of ion-permeable "pores" in membranes.
Kojima
Taiki
T
Department of Gastroenterological Surgery, Aichi Cancer Center, Kanokoden 1-1, Chikusa-ku, Nagoya-shi, Aichi-ken 464-8681, Japan. tkojima@aichi-cc.jp
Fujimitsu
Yasunobu
Y
Kojima
Hiroshi
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000737:chemistry*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010455:Peptides; D013274:Stomach Neoplasms / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001057:Apolipoproteins E; D006131:Growth Inhibitors; D010455:Peptides