Incorporation of network pharmacology, molecular docking, survival, density functional theory, and experimental studies to explore the potential key targets of formononetin by TERT-mediated anti-cancer effects in MCF-7 breast cancer.

Breast cancer remains a significant global health burden, with a rising incidence and mortality rate, particularly among younger women. Despite substantial therapeutic progress, effective molecular targets for treatment remain limited. This study investigated the oncogenic function of telomerase reverse transcriptase (TERT) and assessed the anti-cancer potential of formononetin using integrated bioinformatics and computational analyses. Pharmacokinetic and toxicity profiles were assessed using SwissADME, pkCSM, and Protox-II. Potential drug and disease targets were retrieved from SwissTarget, TargetNet, GeneCards, and DisGeNET databases, identifying 45 overlapping targets. Protein-protein interaction mapping via STRING and topological analysis in Cytoscape highlighted TERT, PIK3CA, ESR1, and KIT as key nodes. Molecular docking revealed high binding affinities of formononetin toward TERT (- 8.15 kcal/mol) and PIK3CA (- 8.01 kcal/mol). Gene expression profiling using GEPIA2 confirmed significant over expression of TERT and PIK3CA in breast carcinoma tissues. Pathway enrichment analysis, conducted through ShinyGO, in conjunction with density functional theory (DFT) calculations, elucidated the electronic and interaction dynamics underlying ligand-target stability. Collectively, these findings suggest that formononetin may be a promising lead compound for targeting TERT-driven breast cancer, warranting further in vivo and clinical validation to establish its therapeutic potential.