Analysis of the drug-target-disease network of trichosanthes-angelica sinensis-frankincense-myrrh in the treatment of breast cancer

Abstract

This study aims to investigate the key bioactive compounds, potential targets, and molecular mechanisms of Trichosanthes-Angelica sinensis-Frankincense-Myrrh (TAFM) in the treatment of breast cancer using network pharmacology and molecular docking methods. The chemical constituents and related targets of TAFM were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. GeneCards, Online Mendelian Inheritance in Man (OMIM), Drugbank, and Therapeutic Target Database (TTD) databases were used to identify breast cancer-related targets. Cytoscape 3.9.1 software and the STRING (Search Tool for the Retrieval of Interaction Gene/Proteins) database were used to visualize the drug component-target-disease and protein interaction networks before screening the core components and key targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID (Database for Annotation, Visualization and Integrated Discovery) database, and molecular docking was performed using AutoDock and PyMOL software. We found that the key active ingredients of TAFM in the treatment of breast cancer include β-sitosterol, stigmasterol, ellagic acid, pelargonidin, and petunidin. A total of 38 key targets and hub genes, including ESR1, VEGFA, PTGS2, HSP90AA1, and CASP3, were identified. Molecular docking results confirmed that stigmasterol and Caspase 3 (CASP3) were the most closely related targets. GO enrichment analysis demonstrated that the biological processes involved mainly included drug response, positive apoptosis process regulation, and two-way gene expression regulation. KEGG pathway analysis revealed the involvement of pathways related to cancer, inflammation, and infection-related diseases. The study results provide supportive evidence that β-sitosterol, stigmasterol, ellagic acid, pelargonidin, and petunidin represent the key bioactive ingredients of TAFM that exhibit anti-breast cancer activity through the regulation of estrogen receptor alpha (ESR1), vascular endothelial growth factor A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), heat shock protein 90 alpha (HSP90AA1), and CASP3 in the treatment of breast cancer.