Exploring the anti-cancer potential of daidzin in breast cancer: Integrated bioinformatics and computational insights...

Breast cancer (BC) remains the most prevalent cancer among women, with high recurrence rates highlighting the urgent need for novel therapeutic strategies. This study evaluates the chemopreventive potential of daidzin, a dietary isoflavone, as a targeted inhibitor of key oncogenic proteins involved in BC progression. Differentially expressed genes (DEGs) between BC cells and normal samples were identified using the GSE85871 dataset. Subsequent pathway enrichment analysis, protein-protein interaction (PPI) network construction, and validation using the TCGA cohort were conducted to elucidate daidzin's regulatory impact. Molecular docking, molecular dynamics (MD) simulations, principle component analysis (PCA), free energy landscape (FEL) analysis, Secondary structure analysis (SSA) and MM-GBSA calculations, including per-residue decomposition, were employed to characterize the binding interactions. Furthermore, the ADMET properties were also conducted for diazin to see the druggability. The analysis revealed 449 upregulated and 644 downregulated genes following daidzin treatment. KEGG pathway enrichment indicated significant downregulation of cancer-associated pathways, including PI3K-Akt signaling, focal adhesion, and cytokine-cytokine receptor interactions. Expression and validation analyses confirmed that daidzin effectively targets and inhibits key oncogenes such as KRAS, CCND1, CDH11, and MDM2, which play crucial roles in BC progression and serve as diagnostic biomarkers. Molecular docking demonstrated favorable binding affinities of daidzin to these oncogenic proteins, while MD simulations, PCA, FEL, SSA and MM-GBSA results confirmed stable and favorable interactions, particularly with KRAS, CCND1, and MDM2. Additionally, frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses revealed high chemical reactivity of daidzin. Additionally, ADMET profiling confirmed favorable drug-like properties and acceptable pharmacokinetic characteristics of daidzin. Overall, this integrated analysis suggests that daidzin could serve as a promising natural agent for breast cancer chemoprevention by targeting and downregulating essential oncogenes and disrupting critical cancer-associated signaling pathways.