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

作者：Au**acher Dominik; Svineng Gunbjorg; Hansen Terkel; Strom Morten B^*

来源：Biochimica et Biophysica Acta-Biomembranes, 2012, 1818(11): 2917-2925.

DOI：10.1016/j.bbamem.2012.07.005

• Antimicrobial peptide
• Anticancer peptide
• Apoptosis
• Beta-amino acid
• Caspases
• Mitochondria

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 (IC50 8.1 mu g/ml) and BAA-2 (IC50 3.8 mu g/ml) on Ramos human Burkitt's lymphoma 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 mitochondrial 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.

• 出版日期2012-11