Integrated Network Pharmacology, Molecular Docking, Molecular Simulation, and In Vitro Validation Revealed the Bioactive Components in Soy-Fermented Food Products and the Underlying Mechanistic Pathways in Lung Cancer

Abstract

Globally, lung cancer remains one of the leading causes of cancer-related mortality, warranting the exploration of novel and effective therapeutic approaches. Soy-fermented food products have long been associated with potential health benefits, including anticancer properties. There is still a lack of understanding of the active components of these drugs as well as their underlying mechanistic pathways responsible for their anti-lung cancer effects. In this study, we have undertaken an integrated approach combining network pharmacology and molecular docking to elucidate the mechanism of action of soy-fermented food products against lung cancer through simulation and in vitro validation. Using network pharmacology, we constructed a comprehensive network of interactions between the identified isoflavones in soy-fermented food products and lung cancer-associated targets. Molecular docking was performed to predict the binding affinities of these compounds with key lung cancer-related proteins. Additionally, molecular simulation was utilized to investigate the stability of the compound–target complexes over time, providing insights into their dynamic interactions. Our results identified daidzein as a potential active component in soy-fermented food products with high binding affinities towards critical lung cancer targets. Molecular dynamic simulations confirmed the stability of the daidzein–MMP9 and daidzein–HSP90AA1 complexes, suggesting their potential as effective inhibitors. Additionally, in vitro validation experiments demonstrated that treatment with daidzein significantly inhibited cancer cell proliferation and suppressed cancer cell migration and the invasion of A549 lung cancer cells. Consequently, the estrogen signaling pathway was recognized as the pathway modulated by daidzein against lung cancer. Overall, the findings of the present study highlight the therapeutic potential of soy-fermented food products in lung cancer treatment and provide valuable insights for the development of targeted therapies using the identified bioactive compounds. Further investigation and clinical studies are warranted to validate these findings and translate them into clinical applications for improved lung cancer management.