Cargando…
Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach
BACKGROUND: The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL/METHODS: Using a web-based platform, all CRC-causing genes were identified using a database...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683728/ https://www.ncbi.nlm.nih.gov/pubmed/31352466 http://dx.doi.org/10.12659/MSM.918250 |
_version_ | 1783442143298191360 |
---|---|
author | Huang, Chen Li, Rong Shi, Wuxiang Huang, Zhaoquan |
author_facet | Huang, Chen Li, Rong Shi, Wuxiang Huang, Zhaoquan |
author_sort | Huang, Chen |
collection | PubMed |
description | BACKGROUND: The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL/METHODS: Using a web-based platform, all CRC-causing genes were identified using a database of gene-disease associations (DisGeNET), and all well-known genes of CC identified using the databases of prediction of protein targets of small molecules (Swiss Target Prediction), drug classification, and target prediction (SuperPred). The carefully selected genes of CRC and CC were concurrently constructed by using a database of functional protein association networks (STRING), and use of software for visualizing complex networks (Cytoscape), characterized with production of protein-protein interaction (PPI) network of CC against CRC. The important biological targets of CC against CRC were identified through topological analysis, then the biological processes and molecular pathways of CC against CRC were further revealed for testing these important biotargets by enrichment assays. RESULTS: We found that the key predictive targets of CC against CRC were estrogen receptor 2 (ESR2), ATP-binding cassette sub-family G member 2 (ABCG2), breast cancer type 1 susceptibility protein (BRCA1), estrogen receptor 1 (ESR1), cytochrome p450 19A1 (CYP19A1), and epidermal growth factor receptor (EGFR). Visual analysis revealed that the biological processes of CC against CRC were positively linked to hormonal metabolism, regulation of genes, transport, cell communication, and signal transduction. Further, the interrelated molecular pathways were chiefly related to endogenous nuclear estrogen receptor alpha network, forkhead box protein A1 (FOXA1) transcription factor network, activating transcription factor 2 (ATF2) transcription factor network, regulation of telomerase, plasma membrane estrogen receptor signaling, estrogen biosynthesis, androgen receptor, FOXA transcription factor networks, estrogen biosynthesis, and phosphorylation of repair proteins. CONCLUSIONS: Use of system pharmacology revealed the biotargets, biological processes, and pharmacological pathways of CC against CRC. Intriguingly, the identifiable predictive biomolecules are likely potential targets for effectively treating CRC. |
format | Online Article Text |
id | pubmed-6683728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66837282019-08-26 Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach Huang, Chen Li, Rong Shi, Wuxiang Huang, Zhaoquan Med Sci Monit Molecular Biology BACKGROUND: The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL/METHODS: Using a web-based platform, all CRC-causing genes were identified using a database of gene-disease associations (DisGeNET), and all well-known genes of CC identified using the databases of prediction of protein targets of small molecules (Swiss Target Prediction), drug classification, and target prediction (SuperPred). The carefully selected genes of CRC and CC were concurrently constructed by using a database of functional protein association networks (STRING), and use of software for visualizing complex networks (Cytoscape), characterized with production of protein-protein interaction (PPI) network of CC against CRC. The important biological targets of CC against CRC were identified through topological analysis, then the biological processes and molecular pathways of CC against CRC were further revealed for testing these important biotargets by enrichment assays. RESULTS: We found that the key predictive targets of CC against CRC were estrogen receptor 2 (ESR2), ATP-binding cassette sub-family G member 2 (ABCG2), breast cancer type 1 susceptibility protein (BRCA1), estrogen receptor 1 (ESR1), cytochrome p450 19A1 (CYP19A1), and epidermal growth factor receptor (EGFR). Visual analysis revealed that the biological processes of CC against CRC were positively linked to hormonal metabolism, regulation of genes, transport, cell communication, and signal transduction. Further, the interrelated molecular pathways were chiefly related to endogenous nuclear estrogen receptor alpha network, forkhead box protein A1 (FOXA1) transcription factor network, activating transcription factor 2 (ATF2) transcription factor network, regulation of telomerase, plasma membrane estrogen receptor signaling, estrogen biosynthesis, androgen receptor, FOXA transcription factor networks, estrogen biosynthesis, and phosphorylation of repair proteins. CONCLUSIONS: Use of system pharmacology revealed the biotargets, biological processes, and pharmacological pathways of CC against CRC. Intriguingly, the identifiable predictive biomolecules are likely potential targets for effectively treating CRC. International Scientific Literature, Inc. 2019-07-28 /pmc/articles/PMC6683728/ /pubmed/31352466 http://dx.doi.org/10.12659/MSM.918250 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Molecular Biology Huang, Chen Li, Rong Shi, Wuxiang Huang, Zhaoquan Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach |
title | Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach |
title_full | Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach |
title_fullStr | Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach |
title_full_unstemmed | Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach |
title_short | Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by Using System Pharmacology Approach |
title_sort | discovery of the anti-tumor mechanism of calycosin against colorectal cancer by using system pharmacology approach |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683728/ https://www.ncbi.nlm.nih.gov/pubmed/31352466 http://dx.doi.org/10.12659/MSM.918250 |
work_keys_str_mv | AT huangchen discoveryoftheantitumormechanismofcalycosinagainstcolorectalcancerbyusingsystempharmacologyapproach AT lirong discoveryoftheantitumormechanismofcalycosinagainstcolorectalcancerbyusingsystempharmacologyapproach AT shiwuxiang discoveryoftheantitumormechanismofcalycosinagainstcolorectalcancerbyusingsystempharmacologyapproach AT huangzhaoquan discoveryoftheantitumormechanismofcalycosinagainstcolorectalcancerbyusingsystempharmacologyapproach |