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Curcumin for gastric cancer: Mechanism prediction via network pharmacology, docking, and in vitro experiments
Peng-Hui Yang1, Ya-Nan Wei1, Bi-Juan Xiao2
1The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China.
Background:
Curcumin originates from the natural herb turmeric, and its antitumor effects have been known about for a long time. However, the mechanism by which curcumin affects gastric cancer (GC) has not been elucidated.
Aim:
To elucidate the potential mechanisms of curcumin in the treatment of GC.
Methods:
Network pharmacological approaches were used to perform network analysis of Curcumin. We first analyzed Lipinski's Rule of Five for the use of Curcumin. Curcumin latent targets were predicted using the PharmMapper, SwissTargetPrediction and DrugBank network databases. GC disease targets were mined through the GeneCard, OMIM, DrugBank and TTD network databases. Then, GO enrichment, KEGG enrichment, protein-protein interaction (PPI), and overall survival analyses were performed. The results were further verified through molecular docking, differential expression analysis and cell experiments.
Results:
We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets. The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways. Following PPI analysis, 6 hub targets were identified, namely, estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6 (CYP2B6). These factors are correlated with decreased survival rates among patients diagnosed with GC. Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes. The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation. mRNA levels of hub targets CYP3A4, MAPK14, CYP1A2, and CYP2B6 in BGC-823 cells were significantly increased in each dose group.
Conclusion:
Curcumin can play an anti-GC role through a variety of targets, pathways and biological processes.
Insights
Curcumin, derived from turmeric, demonstrates anti-gastric cancer (GC) effects by targeting key genes like ESR1 and EGFR. This study elucidates curcumin's therapeutic mechanisms in GC treatment.
Area of Science:
- Pharmacology
- Oncology
- Bioinformatics
Background:
- Curcumin, a natural compound from turmeric, possesses known antitumor properties.
- The precise mechanisms of curcumin's action against gastric cancer (GC) remain largely unelucidated.
Purpose of the Study:
- To investigate the molecular mechanisms underlying curcumin's therapeutic effects in gastric cancer.
- To identify potential molecular targets of curcumin in GC treatment.
Main Methods:
- Network pharmacology approaches were employed, including target prediction and pathway enrichment analysis.
- Key methods involved Lipinski's Rule of Five analysis, target mining from multiple databases, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) analysis, and molecular docking.
- Experimental validation included differential gene expression analysis and cell-based assays.
Main Results:
- A total of 31 overlapping targets between curcumin and GC were identified, enriched in 81 GO biological processes and 22 pathways.
- Six hub genes (ESR1, EGFR, CYP3A4, MAPK14, CYP1A2, CYP2B6) were identified, associated with decreased GC patient survival.
- Curcumin inhibited BGC-823 cell growth and proliferation, with increased mRNA levels of hub genes CYP3A4, MAPK14, CYP1A2, and CYP2B6 observed.
Conclusions:
- Curcumin exhibits anti-gastric cancer activity through a complex network of targets, pathways, and biological processes.
- The identified hub genes represent potential therapeutic targets for curcumin-based GC treatment.
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