Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking
Nitazoxanide has been investigated for colorectal cancer and breast cancer. However, its molecular targets and pathways have not yet been explored for hepatocellular carcinoma (HCC) treatment. Utilizing a network pharmacology approach, nitazoxanide’s potential targets and molecular pathways for HCC...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.968148/full |
| _version_ | 1818189813091663872 |
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| author | Shakeel Ahmad Khan Terence Kin Wah Lee Terence Kin Wah Lee |
| author_facet | Shakeel Ahmad Khan Terence Kin Wah Lee Terence Kin Wah Lee |
| author_sort | Shakeel Ahmad Khan |
| collection | DOAJ |
| description | Nitazoxanide has been investigated for colorectal cancer and breast cancer. However, its molecular targets and pathways have not yet been explored for hepatocellular carcinoma (HCC) treatment. Utilizing a network pharmacology approach, nitazoxanide’s potential targets and molecular pathways for HCC treatment were investigated. HCC targets were extracted from the GeneCards database. Potential targets of nitazoxanide were predicted using Swiss Target Prediction and Super Pred. Intersecting targets were analyzed with VENNY online tool. Using Cytoscape, a protein-protein interaction (PPI), cluster, and core targets-pathways networks were constructed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. The nitazoxanide was molecularly docked with anti-HCC core targets by employing Auto Dock Vina. A total of 168 potential targets of nitazoxanide, 13,415 HCC-related targets, and 153 intersecting targets were identified. The top eight anti-HCC core targets were identified: SRC, EGFR, CASP3, MMP9, mTOR, HIF1A, ERBB2, and PPARG. GO enrichment analysis showed that nitazoxanide might have anti-HCC effects by affecting gene targets involved in multiple biological processes (BP) (protein phosphorylation, transmembrane receptor protein tyrosine kinase (RTKs) signaling pathway, positive regulation of MAP kinase activity, etc.). KEGG pathways and core targets-pathways network analysis indicated that pathways in cancer and proteoglycans in cancer are two key pathways that significantly contribute to the anti-HCC effects of nitazoxanide. Results of molecular docking demonstrated the potential for active interaction between the top eight anti-HCC core targets and nitazoxanide. Our research offers a theoretical basis for the notion that nitazoxanide may have distinct therapeutic effects in HCC, and the identified pharmacological targets and pathways might function as biomarkers for HCC therapy. |
| first_indexed | 2024-12-11T23:48:47Z |
| format | Article |
| id | doaj.art-0bad3be39ef246478e7234638e4e5ee9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T23:48:47Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-0bad3be39ef246478e7234638e4e5ee92022-12-22T00:45:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.968148968148Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular dockingShakeel Ahmad Khan0Terence Kin Wah Lee1Terence Kin Wah Lee2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, ChinaState Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, ChinaNitazoxanide has been investigated for colorectal cancer and breast cancer. However, its molecular targets and pathways have not yet been explored for hepatocellular carcinoma (HCC) treatment. Utilizing a network pharmacology approach, nitazoxanide’s potential targets and molecular pathways for HCC treatment were investigated. HCC targets were extracted from the GeneCards database. Potential targets of nitazoxanide were predicted using Swiss Target Prediction and Super Pred. Intersecting targets were analyzed with VENNY online tool. Using Cytoscape, a protein-protein interaction (PPI), cluster, and core targets-pathways networks were constructed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. The nitazoxanide was molecularly docked with anti-HCC core targets by employing Auto Dock Vina. A total of 168 potential targets of nitazoxanide, 13,415 HCC-related targets, and 153 intersecting targets were identified. The top eight anti-HCC core targets were identified: SRC, EGFR, CASP3, MMP9, mTOR, HIF1A, ERBB2, and PPARG. GO enrichment analysis showed that nitazoxanide might have anti-HCC effects by affecting gene targets involved in multiple biological processes (BP) (protein phosphorylation, transmembrane receptor protein tyrosine kinase (RTKs) signaling pathway, positive regulation of MAP kinase activity, etc.). KEGG pathways and core targets-pathways network analysis indicated that pathways in cancer and proteoglycans in cancer are two key pathways that significantly contribute to the anti-HCC effects of nitazoxanide. Results of molecular docking demonstrated the potential for active interaction between the top eight anti-HCC core targets and nitazoxanide. Our research offers a theoretical basis for the notion that nitazoxanide may have distinct therapeutic effects in HCC, and the identified pharmacological targets and pathways might function as biomarkers for HCC therapy.https://www.frontiersin.org/articles/10.3389/fphar.2022.968148/fullnitazoxanidenetworkpharmacologymolecular dockinghepatocellular carcinoma |
| spellingShingle | Shakeel Ahmad Khan Terence Kin Wah Lee Terence Kin Wah Lee Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking Frontiers in Pharmacology nitazoxanide network pharmacology molecular docking hepatocellular carcinoma |
| title | Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking |
| title_full | Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking |
| title_fullStr | Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking |
| title_full_unstemmed | Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking |
| title_short | Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking |
| title_sort | investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking |
| topic | nitazoxanide network pharmacology molecular docking hepatocellular carcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.968148/full |
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