Bioinformatics Analysis to Screen Key Targets of Curcumin against Colorectal Cancer and the Correlation with Tumor-Infiltrating Immune Cells

Abstract

Purpose. Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking. Methods. The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking, and the correlation between the key targets and tumor-infiltrating immune cells (TICs) was analyzed. Results. A total of 30 potential targets of curcumin for CRC treatment were collected. The GO function enrichment analysis showed 140 items, and the KEGG pathway enrichment analysis showed 61 signaling pathways related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results showed that curcumin could be combined with AKT1, EGFR, and STAT3 more stably, and AKT1 has the strongest binding to curcumin. Bioinformatics analysis discovered that the expression of core targets AKT1, EGFR, and STAT3 in CRC was related to TICs. Conclusion. This study explored the targets and pathways of curcumin in the treatment of CRC. The core targets are AKT1, EGFR, and STAT3. The study indicated that curcumin has preventive and treatment effects on CRC through multitarget and multipathway, which laid the foundation for follow-up research.

Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study

“…Using molecular docking, a study to find possible applicable curcumin targets for treating colorectal cancer showed that curcumin could stably combine with EGFR, STAT3, and AKT1. AKT1, the strongest binding to curcumin, was shown in their study [ 119 ]. In accordance with our study, EGFR with binding affinity energy: −8.9 kcal/mol, STAT3: −7.4 kcal/mol, and AKT1: −6.9 kcal/mol interacted with curcumin.…”

Inhibition and potential treatment of colorectal cancer by natural compounds via various signaling pathways

“…CCM can regulate the activity of the PI3K/Akt signaling pathway by reducing the phosphorylation of Akt, thereby inhibiting the proliferation of CRC cells and promoting apoptosis ( 80 ). The targets and pathways of CCM in the treatment of CRC have been predicted through bioinformatics analysis and molecular docking technology ( 81 ). The core targets are AKT1, the epidermal growth factor receptor (EGFR), and STAT3, with AKT1 exhibiting the strongest binding ability to CCM.…”

“…A recent study found that CCM can inhibit the expression of Nicotinamide N-methyltransferase (NNMT) and p-STAT3 in CRC cells and attenuate NNMT-induced resistance to 5-FU ( 145 ). Bioinformatics analysis identified AKT1, EGFR, and STAT3 as the core targets of CCM in the treatment of CRC ( 81 ). In addition, feruloylacetone, which is naturally degraded after CCM heating, can also significantly inhibit STAT3 phosphorylation and protein expression levels in CRC cells ( 146 ).…”

Curcumin and its nano-formulations: Defining triple-negative breast cancer targets through network pharmacology, molecular docking, and experimental verification

“…Network pharmacology is a powerful tool for systematically exploring the complex pharmacological effects of drugs ( Han et al, 2021 ). By the method of network pharmacology, some traditional Chinese medicines have been reported to suppress cancers.…”