Cyclic Dodecapeptide Induces Cell Death Through Membrane-Peptide Interactions in Breast Cancer Cells

Antimicrobial peptides (AMPS) are present in many organisms ranging from insects to mammals. They have a selectivity as cationic and amphiphilic alpha-helical peptide molecules and might interact with tumor cell membranes. In this study, it was aimed to investigate the anticancer effects of cyclic dodecapeptide (CDP), which is an AMP on MCF-7 and MDA-MB 231 cells from breast cancer cell lines for the first time. Anticancer activity and mechanism of action of CDP were investigated via cancer cell viability assay, cell cytotoxic assay, acridine orange/ethidium bromide dual fluorescence dying assay and scanning electron microscope technique, solid phase heparan sulfate and chondroitin sulfate binding assay, and peptide binding assay. CDP decreases cell viability and induces the death of breast cancer cells by impairing the membrane integrity and causes necrotic cell death by forming pores in the membranes. CDP binds to the negatively charged glycosaminoglycans and shows more affinity against breast cancer cells than fibroblast cells. As a result, the anticancer activity of CDP presented for the first time against breast cancer cells and it has a therapeutic value due to its selective toxicity.