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

Abstract

Abstract Several studies have identified the antibacterial properties of moricin peptides. However, the anticancer potential and, mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. Therefore, using in silico, analytical methods (Reverse Phase-high performance liquid chromatography (RP-HPLC), mass spectroscopy (MS), and circular dichroism (CD), and in vitro studies, an investigation has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. In-silico analysis was performed to predict the anticancer potential of moricin in cancer cells by using AntiCP and ACP servers based on a Support Vector Machine (SVM). Additionally, molecular docking was performed to predict the moricin peptide-related cancer signalling pathway(s). In vitro studies were performed using MDA-MB-231 cells. We observed that moricin exposure at relatively low concentrations (6.25 µg/ml or 1.37µM and 12.5 µg/ml or 2.75µM) to MDA-MB-231 cells caused a higher generation of reactive oxygen species (ROS) (notably superoxide radical (O2•–). Moricin exposure caused down regulation in the expression of Notch-1 and, NFƙB and Bcl2 proteins, while ROS-induced upregulation of P53 caused caspase-dependent cell death in MDA-MB-231 cells. In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in cancer cells.