Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Revealed the Molecular Targets and Potential Mechanism of Nauclea Latifolia in the Treatment of Breast Cancer.

Abstract

Breast cancer (BRCA) incidence is increasing, posing a significant public health challenge and necessitating effective treatment solutions. Nauclea latifolia (N. latifolia) has shown anticancer activity against multidrug-resistant BRCA cells, though its mechanism of action remains unclear. We used online databases Swiss target prediction and GeneCards to identify therapeutic targets for BRCA and active compounds in N. latifolia. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Molecular docking, gene expression and survival analyses of core targets were conducted using Autodock 4.0 and GEPIA2 database. We identified 141 intersecting targets for BRCA and N. latifolia compounds, with key targets including ALB, AKT1, ESR1, STAT3, EGFR, SRC, PTGS2, GSK3B, MMP9, and PPAR1. These targets are involved in cell proliferation and death through pathways such as the PI3K-Akt signaling system, metabolic pathways, cancer pathways, and proteoglycans in cancer. Gene expression and survival analysis indicated these targets as potential markers for BRCA treatment prognosis. This study provides insights into the mechanism of action of N. latifolia against BRCA cells and give a basis to clinicians for future drug development.