Unveiling the mechanism of genistin from Glycine max against breast cancer using computational approaches

Abstract

Breast cancer, a leading cause of morbidity and mortality in women, demands innovative therapeutic solutions. Genistin, an isoflavonoid derived from Glycine max, exhibits promising cytotoxicity against MCF-7 cells; however, its molecular interactions remain unclear. This study investigates the anti-breast cancer mechanisms of genistin using network pharmacology and computational approaches. Through integrated bioinformatics databases, 102 shared targets were identified, with hub genes (TNF, AKT1, SIRT1) elucidated via STRING and Cytoscape protein–protein interaction networks. GO and KEGG analyses highlighted genistin’s modulation of apoptosis and PI3K-Akt pathways. Molecular docking revealed that genistin has a strong binding affinity to SIRT1 (− 10.72 kcal/mol), compared to sirtinol (− 10.56 kcal/mol). Key interactions at Asp272 and His363 enhance active-site stability and specificity, which are critical for modulating tumor cell survival. Molecular dynamics simulations, running for 100 ns, confirmed the stability of genistin-SIRT1, supporting robust binding to SIRT1. MMGBSA analysis showed genistin-SIRT1’s superior binding free energy (− 26.61 kcal/mol) compared to sirtinol (− 20.75 kcal/mol), driven by enhanced van der Waals and electrostatic forces. DFT calculations indicated that genistin has greater chemical stability (ΔE: 10.9274 eV) compared to sirtinol (9.3543 eV). ADMET profiling confirmed genistin’s favorable pharmacokinetics, including non-mutagenicity, low hepatotoxicity, and steady clearance, despite reduced intestinal absorption compared to sirtinol. Genistin exhibited minimal toxicity and high bioactivity, positioning it as a potential candidate for breast cancer therapy via SIRT1 regulation. These findings provide a basis for future in vitro and in vivo studies to refine the therapeutic application of genistin.