Bioinformatics, Molecular Docking Simulation and in vitro Experiments Reveal the Bioactive Compounds and Mechanism of Coptis chinensis Franch. Against Colorectal Adenocarcinoma

Abstract

Background: Coptis chinensis Franch. (CCF) is a Traditional Chinese medicine known for its good anti-cancer effects. However, the bioactive compounds and mechanisms underlying its anti-colorectal adenocarcinoma (COAD) remains unclear.Objectives: This study aims to reveal the bioactive compounds and mechanism of CCF against COAD by utilizing bioinformatics, molecular docking simulation and in vitro experiments.Materials and Methods: Bioactive compounds and candidate targets of CCF against COAD were collected using the Traditional Chinese Medicine Systems Pharmacology Database, Analysis Platform (TCMSP), Gene Expression Omnibus (GEO), Gene Cards, and SwissTargetPrediction databases, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID (v2022q3) database. The “Compounds-Targets-Pathways” (C-T-P) and “Protein-Protein Interaction” (PPI) networks were constructed using Cytoscape (v3.8.0) to identify the hub targets. AutoDock Vina (v1.2.0), UNLCAN, TCGA, MTT, plate cloning, and quantitative real-time PCR (qPCR) assays were used to confirm the results.Results: The “C-T-P” and “PPI” networks revealed three hub targets: checkpoint kinase 1 (CHEK1), polo like kinase 1 (PLK1), and aurora kinase B (AURKB). Molecular docking simulation results showed that berberine, a candidate bioactive compound of CCF, had high affinity with the hub targets, comparable to that of positive drugs. Both CCF ethanol extracts and berberine significantly down-regulated CHEK1, PLK1, and AURKB, inhibited proliferation and promoted apoptosis of HCT-116 cells.Conclusion: To summarize, CCF inhibits COAD by down-regulating CHEK1, PLK1, and AURKB, with berberine as its primary bioactive compound.

Keywords: Coptis chinensis Franch; colorectal adenocarcinoma; bioinformatics; molecular docking simulation; in vitro experiments