Network pharmacology analysis and in vitro experimental validation of liriodenine against non-small cell lung cancer

Liriodenine, a natural aporphine alkaloid from various medicinal plants, has shown antitumor activity in several cancers. However, its role and mechanisms in non-small cell lung cancer (NSCLC) remain unclear. Potential targets of liriodenine and NSCLC were retrieved from public databases. Core targets were identified using random forest and the Least Absolute Shrinkage and Selection Operator regression algorithms. Molecular docking and dynamics simulations assessed the binding affinity and stability between liriodenine and its targets. In vitro assays were performed in A549 cells. Cell viability, proliferation, migration, and apoptosis were evaluated by CCK-8, colony formation, wound healing, and flow cytometry, respectively. Western blot was used to measure Transforming Growth Factor Beta 1(TGF-β1)expression. Sixty-five overlapping targets were identified. Computational analysis showed that liriodenine strongly and stably binds TGF-β1. In vitro, liriodenine significantly inhibited proliferation and migration, induced apoptosis, and downregulated TGF-β1 expression in a dose-dependent manner. These effects provide evidence suggesting the involvement of the TGF-β1/Epithelial-Mesenchymal Transition pathway. This study provides both computational and experimental evidence that liriodenine inhibits the growth and migration of NSCLC cells and promotes apoptosis by suppressing TGF-β1. These findings highlight its potential as a natural candidate for targeted therapy against NSCLC.