Analysis of mechanism of Brucea javanica in the treatment of triple-negative breast cancer
ZHANG Huixian
XU Yongji
ZHAO Yanyan
LI Lanfang
Abstract：Objective To explore the potential mechanism of Brucea javanica in the treatment of triple-negative breast cancer(TNBC)based on network pharmacology and molecular docking and to provide a theoretical basis for the de-velopment of new targets and drugs for TNBC.Methods The active ingredients of Brucea javanica were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of these active ingredients were searched using the SwissTargetPrediction database.TNBC-related targets were obtained through the GeneCards,Therapeutic Target Database(TTD)and Online Mendelian Inheritance in Man(OMIM)databas-es.The active ingredient targets of Brucea javanica and triple-negative breast cancer(TNBC)-related disease targets were intersected.A protein-protein interaction(PPI)network was constructed using the STRING database to identify core thera-peutic targets of Brucea javanica against TNBC.The Metascape database was used for Gene Ontology(GO)functional en-richment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Molecular dock-ing was then employed to evaluate the binding affinity between the primary active ingredients of Brucea javanica and the core targets in TNBC treatment.Results Through the screening of the TCMSP database,18 active ingredients of Brucea javanica and 374 target genes were obtained.After taking the intersection with 1,566 target genes related to TNBC dis-ease,124 potential target genes of Brucea javanica for the treatment of TNBC were obtained.PPI network analysis re-vealed 17 core therapeutic targets of Brucea javanica against TNBC,including AKT1,tumor protein p53(TP53),epider-mal growth factor receptor(EGFR),NFE2L2,prostaglandin-endoperoxide synthase 2(PTGS2),and others.GO analysis revealed that the therapeutic effects of Brucea javanica on TNBC primarily involve the biological processes such as re-sponse to oxidative stress,response to peptides,and positive regulation of kinase activity;they were associated with molec-ular functions including carbonate dehydratase activity,hydrolase activity,and histone kinase activity,and mainly in-volved cellular components such as membrane rafts,membrane microdomains,and integral components of the presynaptic membrane.The KEGG analysis showed that Brucea javanica regulated TNBC mainly through the ferroptosis pathway,pro-teoglycans in cancer pathway and nitrogen metabolism.The molecular docking results demonstrated that 16 core targets could stably bind to the primary active ingredients of Brucea javanica except for mitogen-activated protein kinase 4(MAPK14).Notably,telomerase reverse transcriptase(TERT)and transferrin receptor(TFRC)exhibited higher binding affinity with these ingredients.Conclusion The active ingredients in Brucea javanica,including luteolin,brusatol,and brucine,exert therapeutic effects on TNBC by regulating ferroptosis-related pathways through modulating target proteins such as NFE2L2,TFR1,and MMP9.
Keywords：Brucea javanicatriple-negative breast cancernetwork pharmacologymolecular dockingferroptosis
Publication Date：2025-04-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 32-36 )