Abstract
Natural antimicrobial peptides and ceragenins, as non-peptide amphipathic mimics, have been proposed as anti-cancer agents. To date, it has been confirmed that cathelicidin LL-37 and ceragenin CSA-13, both in free form and immobilized on the surface of magnetic nanoparticles (MNP@LL-37, MNP@CSA-13) induce apoptosis in colon cancer cells. Nevertheless, the question remains whether ceragenins, as synthetic analogs of LL-37 peptide and mimicking a number of its properties, act as antineoplastic agents in breast cancer cells, where LL-37 peptide stimulates oncogenesis. Considering potential anticancer activity, we determined whether CSA-13 and MNP@CSA-13 might be effective against breast cancer cells. Our study provides evidence that both CSA-13 and MNP@CSA-13 decreased viability and inhibit proliferation of MCF-7 and MDA-MB-231 cells despite the protumorigenic properties of LL-37 peptide. Flow cytometry-based analyses revealed that ceragenin treatment results in increases in dead and PI-negative/low-viability cells, which was associated with glutathione (GSH) depletion and increased reactive oxygen species (ROS) generation followed by mitochondrial membrane depolarization, caspase activation, and DNA fragmentation. These findings demonstrate that both CSA-13 and MNP@CSA-13 cause disruption of the oxidative balance of cancer cells. This novel mechanism of ceragenin-mediated eradication of cancer cells suggest that these agents may be developed as a possible treatment of breast cancer.
Highlights
Breast cancer is one of the most prevalent malignancy that affects women worldwide
Our study provides evidence that both cationic steroid antibiotics (CSAs)-13 and magnetic nanoparticles (MNPs)@CSA-13 should be considered as useful pro-apoptotic agents against breast cancer MCF-7 and MDA-MB-231 cells, leading to disruption of cell oxidative balance followed by induction of caspasedependent apoptosis and DNA fragmentation
Ceragenin CSA-13 and MNP@CSA-13 decrease the viability of human breast cancer cells
Summary
According to estimates prepared annually by the American Cancer Society, over 250,000 new cases were expected to be diagnosed in the United States in 2017 [1]. The prevalence of this type of cancer underscores the need for new therapeutic methods and continued analysis of the mechanisms of potential anticancer agents. Research conducted over the past few years has shown that development of breast cancer may be affected by compounds that occur naturally in breast milk and contribute to its anti-infectious properties [3]. The usefulness of human cathelicidin in the treatment of cancer diseases has already been demonstrated in combinatory therapy of ovarian cancer; Chuang et al demonstrated that administration of CpG oligodeoxynucleotides (CpG-ODNs) in the presence of LL-37 enhanced anti-cancer activity of CpG-ODNs against ovarian cancer despite the protumorigenic activity of human cathelicidin in ovarian cancer tissues [16]
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