Therapeutic targets and functions of curcumol against COVID-19 and colon adenocarcinoma

Abstract

Since 2019, the coronavirus disease (COVID-19) has caused 6,319,395 deaths worldwide. Although the COVID-19 vaccine is currently available, the latest variant of the virus, Omicron, spreads more easily than earlier strains, and its mortality rate is still high in patients with chronic diseases, especially cancer patients. So, identifying a novel compound for COVID-19 treatment could help reduce the lethal rate of the viral infection in patients with cancer. This study applied network pharmacology and systematic bioinformatics analysis to determine the possible use of curcumol for treating colon adenocarcinoma (COAD) in patients infected with COVID-19. Our results showed that COVID-19 and COAD in patients shared a cluster of genes commonly deregulated by curcumol. The clinical pathological analyses demonstrated that the expression of gamma-aminobutyric acid receptor subunit delta (GABRD) was associated with the patients' hazard ratio. More importantly, the high expression of GABRD was associated with poor survival rates and the late stages of COAD in patients. The network pharmacology result identified seven-core targets, including solute carrier family 6 member 3, gamma-aminobutyric acid receptor subunit pi, butyrylcholinesterase, cytochrome P450 3A4, 17-beta-hydroxysteroid dehydrogenase type 2, progesterone receptor, and GABRD of curcumol for treating patients with COVID-19 and COAD. The bioinformatic analysis further highlighted their importance in the biological processes and molecular functions in gland development, inflammation, retinol, and steroid metabolism. The findings of this study suggest that curcumol could be an alternative compound for treating patients with COVID-19 and COAD.

Keywords: COVID-19; bioinformatics; biological functions; colon adenocarcinoma; curcumol; pharmaceutics targets.

Figure 1

Network pharmacology identified the targets of curcumol against COVID-19 and colon adenocarcinoma. (A) Right panel: venn diagram shows the number of common targets of curcumol, COVID-19, and colon adenocarcinoma. Left panel: protein–protein interaction of curcumol's target against COVID-19 and colon adenocarcinoma. (B) Volcano plot shows the differentially expressed genes in colon adenocarcinoma targeted by curcumol. The blue dots represent the downregulated genes; the red dots represent the upregulated genes. (C) Cytoscape analysis highlights the protein–protein interaction of curcumol's core targets against COVID-19 and colon adenocarcinoma.

Figure 2

Clinicopathological analysis of curcumol's targets against COVID-19 and colon adenocarcinoma. (A) Survival analysis using the Kaplan–Meier estimator showed that the colon adenocarcinoma patients with higher expression of GABRD had poorer overall survival rates. Higher expressions of GABRD in colon adenocarcinoma patients are associated with (B) advanced stages, (C) metastatic tumors, and (D) a higher number of tumors spread to the lymph nodes. M0 means cancer has not spread to distant organs. M1 means cancer has spread to distant organs. N represents the number of lymph nodes containing the tumor.

Figure 3

Functional characterization of curcumol's targets against COVID-19 and colon adenocarcinoma. The bubble plot highlights the involvement of curcumol's targets in biological processes related to (A) fat and steroid hormone biosynthesis, (B) gland development, and (C) steroid binding and ion channel activity. (D) Gene ontology showed the occurred cell components. (E) KEGG enrichment analysis showed the contribution of curcumol's targets in cell signaling pathways of carcinogenesis. The size of the bubble represents the number of genes. The color of the bubble represents the significance of the terms.

Figure 4

Curcumol treatment inhibited cell proliferation of colon adenocarcinoma and altered the expression of BCHE and CYP3A4. (A) MTT assay showed significant dose-dependent inhibition of cell proliferation in lung adenocarcinoma cell A594 caused by curcumol treatments (0–75 μM). (B) Immunofluorescence staining showed that the treatment of curcumol induced the expression of BCHE and reduced the expression of CYP3A4 in COAD cell, as compared to the control group. *p < 0.05.