Exploring the multifaceted therapeutic potential of linalool in triple negative breast cancer integrating in vitro, in silico, and network pharmacology approaches

A very aggressive type of breast cancer is triple-negative breast cancer (TNBC), leading to few treatment options, poor prognosis, and overall survival. The current trend in the application of natural compounds, especially essential oils, is an appropriate therapeutic approach with low toxicity against cancer. The main objective of the current study was to explore the anticancer activity and potential inhibitory mechanism of linalool, a monoterpene essential oil, in TNBC by using an integrated in vitro and in silico approach. Linalool showed moderate cytotoxicity, with approximately 30% inhibition of TNBC cells’ viability at 100 µg/mL. Moreover, dose-dependent activity was observed in both the anti-inflammatory and antioxidant assays, with the DPPH radical-scavenging assay showing an IC₅₀ value of 51.87 ± 0.56 µg/mL.The in silico network pharmacology approach used SuperPred and GeneCard, which identified 34 common targets of linalool and TNBC, reduced from 128 and 476 targets, respectively. A compound-target-pathway network was built using the cytohubba plugin of Cytoscape software to analyze the hub genes. These targets were further analyzed for gene ontology and KEGG pathway enrichment, emphasizing the relevance of the targets to cancer pathways. Furthermore, the in silico docking study showed good binding affinity of linalool against TOP2A (-5.108 kcal/mol), COX-1 (-5.345 kcal/mol), and NRF-2 (-3.329 kcal/mol) The molecular dynamics simulations highlighted the conformational stability and flexibility of linalool in a real-time dynamic setting. Conclusively, these findings suggested that linalool may modulate TNBC-related molecular pathways and could be considered as a promising preliminary candidate for TNBC requiring future mechanistic and functional validation.