Network Pharmacological Analysis and Experimental Verification of the Anti-hepatocellular Carcinoma Activity and Mechanism of Sesamolin

Abstract

This study aimed to investigate the anti-tumor effect of sesamolin (SES) on hepatocellular carcinoma (HCC) and its molecular mechanism using network pharmacology and experimental verification. The intersecting targets between SES and HCC and their signaling pathways and biological processes were predicted by network pharmacological analysis. The pharmacokinetics properties of SES were analyzed through search against the SwissADME database. The cell count kit-8 (CCK-8) method was used to detect the cell viability. Annexin V-FITC/PI double staining, flow cytometry, Western blotting and cell migration assays were used to analyze the effect and mechanism of SES on cell apoptosis, cell cycle arrest and migration inhibition in Huh-7 cells. The results showed that a total of 64 intersecting targets, 352 gene ontology (GO) functions and 136 Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were identified by network pharmacological analysis. The in vitro test showed that SES induced mitochondria-dependent apoptosis and G2/M phase arrest in Huh-7 cells through regulating the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription-3 (STAT3)/nuclear factor κB (NF-κB) and phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways mediated by reactive oxygen species (ROS). Meanwhile, SES inhibited cell migration through the ROS-mediated PI3K/AKT/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. Finally, SwissADME analysis showed that the SES exhibited excellent druglike properties. In conclusion, sesamolin could induce apoptosis, cell cycle arrest and inhibit migration in Huh-7 cells through the ROS-mediated signaling pathways.

Keywords

• sesamolin; hepatocellular carcinoma; network pharmacology; cell apoptosis; cell cycle; cell migration