Medicinal Food Homology in Action: Flos Sophorae Immaturus-Broccoli Seed Extract Suppresses Tumor Growth through G2/M Arrest and EMT Inhibition

Despite advancements in cancer therapy, metastasis and chemoresistance remain critical challenges due to tumor heterogeneity and compensatory pathways. This study investigates the synergistic anti-tumor potential of Flos Sophorae Immaturus (FSI) and broccoli seed extract (BSE), two natural products aligned with the "medicinal food homology" paradigm. Using in vitro and in vivo models of lung and prostate cancers, we demonstrate that FSI-BSE (F/B extract) co-treatment exerts supra-additive effects by concurrently inducing G2/M cell cycle arrest and suppressing epithelial-mesenchymal transition (EMT). Mechanistically, with integrative LC-MS/MS, network pharmacology, molecular docking, transcriptomic profiling, and molecular experimental validation, this study revealed that F/B extract targets and disrupts the cell cycle regulators such as cyclin-dependent kinases (CDKs) and cell division cycle 25 (CDC25), as well as the EMT effectors (e.g., Matrix metalloproteinase, Snail, and E-cadherin). Additionally, F/B extract suppressed tumor growth without toxicity in xenograft mouse models, supported by unaltered organ histology and blood parameters. These findings demonstrate a polypharmacological strategy leveraging dietary botanicals to address cancer complexity. By bridging cell cycle arrest and EMT inhibition, F/B extract treatment offers a non-toxic adjuvant approach with translational potential, underscoring the therapeutic value of medicinal food homology in oncology.