Exploring the mechanism of Levistolide A in the treatment of lung cancer cells based on network analysis, molecular docking and experimental validation

Levistolide A (LA) is the main active ingredient in the Angelica sinensis (Oliv.) Diels, which has been proved to have therapeutic effects on a variety of tumors, but its role in treating lung cancer remains unreported. In this study, we found that LA can inhibit lung cancer cell lines (A549 and H1299) proliferation and induced apoptosis via CCK-8, plate cloning, EdU labeling, flow cytometry and western blotting assay. Then, network analysis was performed to elucidate the molecular mechanisms of LA in treating lung cancer, we screened and obtained 57 common targets and 14 core targets for LA treatment of lung cancer by PharmMapper, Swiss Target Prediction, GeneCards and OMIM databases. Molecular docking studies demonstrated strong binding of LA to the core targets. KEGG analysis highlighted involvement in “pathways in cancer” and PI3K/AKT signaling. LA increased intracellular ROS levels, which inactivated PI3K/AKT, resulting in apoptosis and growth inhibition via experimental verification. In addition, 740YP (a PI3K/AKT pathway activator) and NAC (a ROS scavenger) were able to reverse the effects of LA on PI3K/AKT pathway, proliferation and apoptosis in lung cancer cells. In conclusion, these findings highlight the potential of LA as a promising anti-lung cancer agent and provide a foundation for further investigation into its clinical applications.