Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the second leading cause of cancer-related death in the world. Plumbagin (PL) is a small molecule naphthoquinone compound isolated from Plumbago zeylanica L. that has important anticancer properties, but its mechanism requires further investigation. In this study, we used a comprehensive network pharmacology approach to study the mechanism of action of PL for the treatment of HCC. The method includes the construction of multiple networks; moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify biological processes and signaling pathways. Subsequently, in vitro experiments were performed to verify the predicted molecular mechanisms obtained from the network pharmacology-based analysis. Network pharmacological analysis showed that PL may exert anti-HCC effects by enhancing reactive oxygen species (ROS) production to generate oxidative stress and by regulating the PI3K/Akt and MAPK signaling pathways. In vitro experiments confirmed that PL mainly mediates the production of ROS, regulates the PI3K/Akt and MAPK signaling pathways to promote apoptosis and autophagy, and shows significant therapeutic effects on HCC. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the potential mechanism of PL for the treatment of HCC.