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Anti-tumor activity of an antibiotic peptide derived from apoprotein E
Taiki Kojima1, Yasunobu Fujimitsu, Hiroshi Kojima
1Department of Gastroenterological Surgery, Aichi Cancer Center, Kanokoden 1-1, Chikusa-ku, Nagoya-shi, Aichi-ken 464-8681, Japan. tkojima@aichi-cc.jp
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.
Insights
The apoprotein E (apoE) 133-162 peptide demonstrates significant anti-tumor activity against various cancer cell lines. This peptide likely functions by disrupting cell membranes, offering a potential new avenue for cancer therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- A 30-mer peptide derived from apoprotein E (apoE) 133-162 previously showed potent antibiotic activity.
- This study investigates the potential anti-tumor properties of the apoE 133-162 peptide.
Purpose of the Study:
- To evaluate the cytotoxic effects of apoE 133-162 on human cancer cell lines.
- To explore the mechanism of action of apoE 133-162 in cancer cells.
Main Methods:
- Cytotoxicity was assessed using MTT assays on gastric, pancreatic, and colon cancer cell lines.
- Membrane perturbation activity was evaluated through calcein leakage assays using artificial liposomes with varying compositions.
Main Results:
- ApoE 133-162 exhibited dose-dependent cytotoxic activity against all tested cancer cell lines.
- The peptide showed comparable activity to 5-FU in Paca-2 cells, without synergistic effects or inhibition by heparin.
- Cholesterol attenuated membrane perturbation, while acidic membranes were more susceptible to lysis by apoE 133-162.
Conclusions:
- ApoE 133-162 possesses significant anti-tumor activity.
- The mechanism likely involves membrane perturbation and the formation of ion-permeable pores.
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