Kurarinone's synergistic target space and therapeutic promise for esophageal squamous cell carcinoma are revealed by systems pharmacology

Background One of the most prevalent cancers in China is esophageal cancer. Rad ix Sophorae flavescentis, a herbal medicine, has been used to treat esophageal cancer in China. Kurarinone is the key bioactive component of Rad ix Sophorae flavescentis; however, its mechanism of action is unclear. Methods In this study, we investigated the mechanism of action of kurarinone in esophageal squamous cell carcinoma (ESCC) through network pharmacology, which involved pharmacokinetics evaluation, active compound screening, drug–target and protein–protein interaction analyses, target protein enrichment analysis, and molecular docking verification. We verified the findings using cell viability and apoptotic assays, as well as Transwell migration–invasion assays. The levels of proteins were examined by western blotting. Results We identified 31 potentially active molecules (e.g., matrine and kurarinone), 113 targets (e.g., TP53 and AKT), and 20 pathways (e.g., PI3K-AKT signaling pathway, lipid synthesis pathways) and carried out molecular docking on the proteins. In vitro experiments showed that kurarinone could increase FAS and CASP3 significantly, decrease the anti-apoptotic protein BCL-2 and increase the pro-apoptotic protein BAX. Flow cytometry showed that kurarinone could induce apoptosis of Eca109 and KYSE150 cells. Conclusion We can conclude that kurarinone can affect esophageal cancer by inhibiting cell proliferation, promoting apoptosis, and inhibiting cancer cell invasion, and thus, metastasis.