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

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 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.