Determining novel candidate anti-hepatocellular carcinoma drugs using interaction networks and molecular docking between drug targets and natural compounds of SiNiSan

Abstract

Background SiNiSan (SNS) is an ancient traditional Chinese medicine (TCM) used to treat liver and spleen deficiencies. We studied the unique advantages of using SNS to treat hepatocellular carcinoma (HCC) with multiple components and targets to determine its potential mechanism of action. Methods The active compounds from the individual herbs in the SNS formula and their targets were mined from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). HCC-associated targets were collected from the TCGA and GEO databases and samples were collected from patients with stage III hepatocellular carcinoma. A compound-disease target network was constructed, visualized, and analyzed using Cytoscape software. We built a protein-protein interaction (PPI) network using the String database. We enriched and analyzed key targets using GSEA, GO, and KEGG in order to explore their functions. Autodock software was used to simulate the process of SNS molecules acting on HCC targets. Results A total of 113 candidate compounds were taken from SNS, and 64 of the same targets were chosen from HCC and SNS. The predominant targets genes were PTGS2, ESR1, CHEK1, CCNA2, NOS2 and AR; kaempferol and quercetin from SNS were the principal ingredients in HCC treatment. The compounds may work against HCC due to a cellular response to steroid hormones and histone phosphorylation. The P53 signaling pathway was significantly enriched in the gene set GSEA enrichment analysis and differential gene KEGG enrichment analysis. Conclusions Our results showed that the SNS component has a large number of stage III HCC targets. Among the targets, the sex hormone receptors, the AR and ESR1 genes, are the core targets of SNS component and the most active proteins in the PPI network. In addition, quercetin, which has the most targets, can act on the main targets (BAX, CDK1, CCNB1, SERPINE1, CHEK2, and IGFBP3) of the P53 pathway to treat HCC.

A systematic study on the treatment of hepatitis B-related hepatocellular carcinoma with drugs based on bioinformatics and key target reverse network pharmacology and experimental verification

“…The representative component quercetin was selected for experimental verification, and it was found that quercetin inhibited the proliferation of HepG2.2.15 cells and Hep3B cells, and reduced the expression levels of CDK1. Similarly, studies showed that quercetin reduced the expressions of CDK1 [ 60 ], and inhibited the proliferation of liver cancer [ 61 ]. Terpenoids and glycosides include celastrol and ursolic acid.…”

Molecular and genetic markers in hepatocellular carcinoma: In silico analysis to clinical validation (current limitations and future promises)

“…A recent study used both molecular docking and genetic networks to design anti-HCC drugs from an ancient traditional Chinese medicine SiNiSan (SNS). SNS affects primarily the p53 pathway, thus regulating apoptosis[ 71 ].…”

Research progress on natural products against hepatocellular carcinoma

“…Natural products have the characteristics of multiple compounds, targets, and pathways when applied in disease prevention and treatment. Molecular docking technology can simulate the results of drug-target interactions [63], making it easier to screen for anticancer drugs. At present, flavonoids [64][65][66], alkaloids, phenolic alcohols [67], and other TCM extracts in natural products have been found to exhibit strong anti-cancer activity in HCC treatment.…”