Target prediction and potential application of dihydroartemisinin on hepatocarcinoma treatment

Abstract Purpose With high incidence of hepatocarcinoma and limited effective treatments, most patients suffer in pain. Anti-tumor drugs are single-targeted, toxicity, causing adverse side effects and resistance. Dihydroartemisinin(DHA) inhibits tumor through multiple mechanisms effectively. This study explores and evaluates afety and potential mechanism of DHA towards human hepatocarcinoma based on network pharmacology in a comprehensive way. Methods Adsorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of DHA were evaluated with pkCSM, SwissADME and ADMETlab. Potential targets of DHA were obtained from SwissTargetPrediction, Drugbank, TargetNET and PharmMapper. Target gene of hepatocarcinoma were obtained from OMIM, GeneCards and DisGeNET. Overlapping targets and hub genes were identified and analyzed for GO, KEGG and Reactome pathway. Molecular docking was utilized to investigate the interactions sites and hydrogen bonds. CCK8, wound healing, invasion and migration assays on HepG2 and SNU387 cell proved DHA inhibits malignant biological features of hepatocarcinoma cell. Results DHA is safe and desirable for clinical application. A total of 131 overlapping targets were identified. Biofunction analysis showed targets were involved in kinase activity, protein phosphorylation, intracellular reception, signal transduction, transcriptome dysregulation, PPAR pathway and JAK-STAT signaling axis. Top 9 hub genes were obtained using MCC algorithm, namely CDK1, CCNA2, CCNB1, CCNB2, KIF11, CHEK1, TYMS, AURKA and TOP2A. Molecular docking suggests that all hub genes form a stable interaction with DHA for optimal binding energy were all less than − 5 kcal/mol. Conclusions Dihydroartemisin might be a potent and safe anticarcinogen based on its biological safety and effective therapeutic effect.