Anticancer mechanisms of action of two small amphipathic beta~2-amino acid derivatives derived from antimicrobial peptides

摘要

We have recently discovered that small antimicrobial (beta~(2,2)-amino acid derivatives (Mw<500) also display activity against cancer cells. To explore their drug potential, we have presently investigated the mechanisms of action of two derivatives BAA-1 (IC_(50) 8.1 mug/ml) and BAA-2 (IC_(50) 3.8 ng/ml) on Ramos human Burkitt's lym-phoma cells. Studies using annexin-V-FITC/propidium iodide staining and flow cytometry revealed essential mechanistic differences, which was confirmed by screening for active caspases, investigation of mitochondri-al membrane potential, and electron microscopy studies. Our results indicated that BAA-1 killed Ramos cells by destabilizing the cell membrane, whereas BAA-2 caused apoptosis by the mitochondrial-mediated pathway.