Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway.

ABSTRACT

BACKGROUND: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. METHODS: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells. RESULTS: In silico observation revealed that moricin is a potential anticancer peptide, and protein-protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ƙB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells. CONCLUSIONS: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug.