Mechanistic research on the anti-hepatocellular carcinoma effect of kurarinone based on network pharmacology and experimental validation

Kurarinone is a potential natural compound with antitumour activity. The effect and mechanism of kurarinone against hepatocellular carcinoma (HCC) remain unclear. Network pharmacology and molecular docking were applied to characterize the mechanism of kurarinone against HCC. The potential targets of kurarinone were mapped with HCC-related targets to probe the candidate proteins of kurarinone against HCC. The potential signaling pathways related to proteins were assessed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Molecular docking was performed to validate the binding energy between kurarinone and core targets. The effect and potential underlying mechanisms of kurarinone on HCC were experimentally validated in HepG2 cells. There were 27 targets of kurarinone against HCC. The interleukin-17 signaling pathway was mostly enriched after pathway enrichment analysis. Molecular docking analysis revealed good affinity between kurarinone and the hub targets. Kurarinone significantly inhibited HepG2 cell viability and cell migration in a dose-dependent manner. The expression levels of two proteins enriched in the interleukin-17 signaling pathway, S100 calcium binding protein A9 (S100A9) and mitogen-activated protein kinase 1 (MAPK1), were downregulated after stimulation with different concentrations of kurarinone in HepG2 cells. Network pharmacology along with molecular docking and experimental validation provided a useful approach for understanding the pharmacological mechanism and therapeutic drug development of kurarinone in HCC.