Influence of Fatty Acid Modification on the Anticancer Activity of the Antimicrobial Peptide Figainin 1

Abstract

Antimicrobial peptides derived from the skin secretions of amphibians have made important progress in tumor therapy due to their unique mechanism of destroying cell membranes. Figainin 1 (F1) is an 18-amino acid antimicrobial peptide from the skin secretions of Boana raniceps frogs. In a previous study, F1 was shown to inhibit cancer cell proliferation. F1 is composed entirely of natural amino acids; therefore, it is easily degraded by a variety of proteases, resulting in poor stability and a short half-life. In the present study, we used a fatty acid modification strategy to improve the stability of Figainin 1. Among the 8 peptides synthesized, A-10 showed the strongest antiproliferative activity against K562 cells and the other four tumor cell lines, and its stability against serum and proteinase K was improved compared with F1. We found that A-10 works through two mechanisms, cell membrane destruction and apoptosis, and can arrest the cell cycle in the G0/G1 phase. Moreover, A-10 exhibited self-assembly behavior. Overall, it is necessary to select a fatty acid with a suitable length for modification to improve the stability and antiproliferative activity of antimicrobial peptides. This study provides a good reference for the development of antimicrobial peptides as effective anticancer compounds.

Figure 1

Cytotoxic efficiency of the peptides at 10 μM on MCF-7 cells and K562 cells.

Figure 2

Mechanism of peptide inhibiting cancer cell proliferation. (A) 10 μM peptide induces 24 h LDH leakage in K562 cells. (B) Apoptosis in K562 cells induced by 10 μM peptide.

Figure 3

Detection of K562 cell cycle and ROS by flow cytometry. (A) Flow cytometry test of 10 μM peptide for 24 h on K562 cells cycle. (B) Effect of 10 μM peptide on ROS of K62 cells tested by flow cytometry for 24 h.

Figure 4

Peptide self-assembly test and stability test. (A) Microplate reader measures the fluorescence of ANS relative to the peptide concentration. (B) Detection of peptide stability to serum by a microplate reader. (C) Detection of peptide stability to proteinase K by a microplate reader.