Background and Aims: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. In this regard, Chinese herbal medicines, Brucea javanica, Centipeda minima, and Lithospermum erythrorhizon have exhibited anti-TNBC effects in both cell culture and mouse models, yet a comprehensive understanding of their mechanisms of action remains elusive. Our study utilized a network pharmacology approach and molecular docking to elucidate potential pivotal pathways, drug targets, and the most efficacious active constituents of these medications in the treatment of TNBC.
Material and Methods: The active compounds and their corresponding target genes were obtained from the TCMSP database. The potential target genes associated with TNBC were also collected from DisGENet. The PPI network was established in the STRING database. The gene ontology and pathway enrichment analyses were conducted using the DAVID platform. AutoDock Vina was used for molecular docking.
Results: The AGE-RAGE signaling pathway in diabetic complications, PI3K-AKT, p53 and MAPK were identified as the top key signaling pathways. The top target proteins included AKT1, TP53, CASP3, and VEGFA. The top active ingredients were also stigmasterol, beta-sitosterol, nobiletin, quercetin, and acetylshikonin which resulted from the disease-drug-compound-target network. The docking results showed good binding affinities ranging from -9 to -6 kcal/mol for all the complexes.
Conclusion: The results highlight the potential of these herbal drugs in TNBC treatment; however, further investigations are needed to validate these findings.