Anti-hepatic carcinoma mechanisms of calycosin through targeting ferroptosis

Abstract

Background: Ferroptosis, a pathologic state induced by lipid-driven oxidative stress, is associated with the development of human cancers. Calycosin, a natural compound with antioxidant and anti-inflammatory activities, has promising antitumor effects. However, the ferroptosis-related mechanism of calycosin in the treatment of hepatic carcinoma has not been reported. Methods: This study applied network pharmacology and bioinformatic approaches (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis) to investigate the pharmacologic targets and mechanism of action of calycosin in the treatment of hepatic carcinoma through targeting ferroptosis. By searching online databases including The Cancer Genome Atlas, FerrDb, GeneCards, SwissTargetPrediction, SuperPred, BindingDB, TargetNet, BATMAN-TCM, and Drugbank, we identified 13 ferroptosis-related putative target genes of calycosin against hepatic carcinoma including IL-6, PTGS2, SRC, HRAS, NQO1, NOX4, PGK1, G6PD, GPI, MIF, NOS2, ALDOA, and SQSTM1. Results: Molecular docking analysis revealed that calycosin potentially binded directly with the target proteins IL-6, PTGS2, and SRC. Functional enrichment analysis of these proteins indicated that they were involved in gluconeogenesis and apoptosis through regulation of ERK1, ERK2, and MAPK activities (P < 0.05). Conclusion: Calycosin exerts antitumor effects in hepatic carcinoma by targeting ferroptosis through regulation of IL-6, PTGS2, and SRC.

Keywords

• Hepatic carcinoma
• Ferroptosis
• Calycosin
• Bioinformatics
• Pharmacologic target