PMID- 31352466
OWN - NLM
STAT- MEDLINE
DCOM- 20200214
LR  - 20210816
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 Jul 28
TI  - Discovery of the Anti-Tumor Mechanism of Calycosin Against Colorectal Cancer by 
      Using System Pharmacology Approach.
PG  - 5589-5593
LID - 10.12659/MSM.918250 [doi]
AB  - 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 AND 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.
FAU - Huang, Chen
AU  - Huang C
AD  - Department of Medical Statistics and Epidemiology, College of Public Health, 
      Guilin Medical University, Guilin, Guangxi, China (mainland).
AD  - Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Songkhla, 
      Thailand.
FAU - Li, Rong
AU  - Li R
AD  - Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin 
      Medical University, Guilin, Guangxi, China (mainland).
FAU - Shi, Wuxiang
AU  - Shi W
AD  - Health Management Unit, Faculty of Humanities and Management, Guilin Medical 
      University, Guilin, Guangxi, China (mainland).
FAU - Huang, Zhaoquan
AU  - Huang Z
AD  - Health Management Unit, Faculty of Humanities and Management, Guilin Medical 
      University, Guilin, Guangxi, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20190728
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (BRCA1 Protein)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ESR1 protein, human)
RN  - 0 (ESR2 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Isoflavones)
RN  - 0 (Neoplasm Proteins)
RN  - 09N3E8P7TA (7,3'-dihydroxy-4'-methoxyisoflavone)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 1.14.14.1 (CYP19A1 protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - Aromatase/genetics
MH  - BRCA1 Protein/genetics
MH  - Biomarkers, Tumor/genetics
MH  - Colonic Neoplasms/genetics
MH  - Colorectal Neoplasms/*genetics/*metabolism/physiopathology
MH  - Computational Biology/methods
MH  - Databases, Genetic
MH  - ErbB Receptors/genetics
MH  - Estrogen Receptor alpha/genetics
MH  - Estrogen Receptor beta/genetics
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Gene Regulatory Networks/genetics
MH  - Isoflavones/*metabolism/pharmacology
MH  - Neoplasm Proteins
MH  - Pharmacological and Toxicological Phenomena
MH  - Protein Interaction Maps/genetics
MH  - Signal Transduction
MH  - Systems Analysis
PMC - PMC6683728
COIS- Conflict interest None.
EDAT- 2019/07/29 06:00
MHDA- 2020/02/15 06:00
PMCR- 2019/07/28
CRDT- 2019/07/29 06:00
PHST- 2019/07/29 06:00 [entrez]
PHST- 2019/07/29 06:00 [pubmed]
PHST- 2020/02/15 06:00 [medline]
PHST- 2019/07/28 00:00 [pmc-release]
AID - 918250 [pii]
AID - 10.12659/MSM.918250 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 Jul 28;25:5589-5593. doi: 10.12659/MSM.918250.