Mechanism of morusin on breast cancer via network pharmacology and in vitro experiments

Abstract

Background: This study aimed to investigate the therapeutic effect of morusin on breast cancer and decode its underlying molecular mechanism using network pharmacology and in vitro techniques. Methods: Swiss Target Prediction and PharMmapper were applied to screen morusin targets. The targets of human breast cancer were obtained from the GeneCards database, and the overlapping targets were screened. A protein-protein interaction network was constructed based on the overlapping targets by String and Cytoscape. Performed Gene Ontology enrichment as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the shared targets of the drug and disease using the David database. Additionally, performed molecular docking using PyMoL and AutoDock software. Finally, the impact of morusin on breast cancer was demonstrated by cell experiments and western blot. Results: A total of 101 target genes were obtained through screening including ESR1, EGFR, ALB, CTNNB1, AKT1, and so on. Based on the annotation of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, the anticancer properties of morusin are linked to apoptosis, migration, and PI3K-AKT signaling pathways. Molecular docking showed an interaction between morusin and PIK3CA, AKT1. In vitro data demonstrated that morusin causes apoptosis and inhibits cell migration. Morusin also increased the expression of cleaved-PARP while decreasing the expression of p-PI3K and p-AKT. Conclusion: Through network pharmacology analysis and in vitro experiments, this study showed that morusin promotes apoptosis and inhibits migration by modulating the PI3K-AKT axis. Morusin plays a key role in the treatment of breast cancer.