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.

Rutin Linoleate Triggers Oxidative Stress-Mediated Cytoplasmic Vacuolation in Non-Small Cell Lung Cancer Cells

“…Our previous computational estimations regarding their properties indicated a higher lipophilicity (cLogP) and lower solubility for RUT-O and RUT-L compared to their parent compound RUT, which is in agreement with the data presented in the literature [10]. A similar correlation between the modification of compounds with fatty acids, their hydrophobicity, and ability to disrupt cell membranes was found in a study conducted by Han and collaborators [35]. Viskupicova et al showed that the conjugation of RUT with fatty acids leads to compounds with increased hydrophobicity and solubility in fats, and presented several works indicating that RUT lipophilic derivatives present better bioavailability and crossing through biological membranes [36].…”