Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer
Abstract Background Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action. Me...
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BMC
2024-09-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-024-00928-2 |
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| author | Zhixuan Wu Haoyi Xiang Xiaowu Wang Rongrong Zhang Yangyang Guo Liangchen Qu Jingyao Zhou Yanyi Xiao |
| author_facet | Zhixuan Wu Haoyi Xiang Xiaowu Wang Rongrong Zhang Yangyang Guo Liangchen Qu Jingyao Zhou Yanyi Xiao |
| author_sort | Zhixuan Wu |
| collection | DOAJ |
| description | Abstract Background Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action. Methods We employed weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the GeneCards database to identify potential targets for TNBC. Simultaneously, we utilized the Swiss Target Prediction, ChEMBL, and STITCH databases to identify potential targets of nomilin. The core targets and mechanisms of nomilin against TNBC were predicted through protein-protein interaction (PPI) network analysis, molecular docking, and enrichment analysis. The results of the network pharmacology were corroborated by conducting experiments. Results A total of 17,204 TNBC targets were screened, and 301 potential targets of nomilin were identified. Through the PPI network, eight core targets of nomilin against TNBC were pinpointed, namely BCL2, Caspase3, CyclinD1, EGFR, HSP90AA1, KRAS, PARP1, and TNF. Molecular docking, molecular dynamics simulation and proteome microarray revealed that nomilin exhibits strong binding activity to these core proteins. Enrichment analysis results indicated that the anti-TNBC effect of nomilin is associated with PI3K/Akt pathway. In vitro and in vivo experiments have demonstrated that nomilin inhibits TNBC cell proliferation and migration while promoting cell apoptosis through the PI3K/Akt pathway. Conclusion For the first time, the research effectively discovered the objectives and mechanisms of nomilin in combating TNBC using network pharmacology, molecular docking, molecular dynamics simulation, proteome microarray and experimental confirmation, presenting a hopeful approach for treating TNBC. Graphical Abstract |
| format | Article |
| id | doaj-art-b75a4f49b79a46d5a836e307fb36b622 |
| institution | OA Journals |
| issn | 1528-3658 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-b75a4f49b79a46d5a836e307fb36b6222025-08-20T02:17:50ZengBMCMolecular Medicine1528-36582024-09-0130112110.1186/s10020-024-00928-2Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancerZhixuan Wu0Haoyi Xiang1Xiaowu Wang2Rongrong Zhang3Yangyang Guo4Liangchen Qu5Jingyao Zhou6Yanyi Xiao7Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical UniversityZhejiang University School of MedicineDepartment of Burns and Skin Repair Surgery, The Third Affiliated Hospital of Wenzhou Medical UniversityZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical UniversityZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical UniversityEmergency Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical UniversityPharmacy Department, Taizhou Central HospitalThe Dingli Clinical College of Wenzhou Medical UniversityAbstract Background Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action. Methods We employed weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the GeneCards database to identify potential targets for TNBC. Simultaneously, we utilized the Swiss Target Prediction, ChEMBL, and STITCH databases to identify potential targets of nomilin. The core targets and mechanisms of nomilin against TNBC were predicted through protein-protein interaction (PPI) network analysis, molecular docking, and enrichment analysis. The results of the network pharmacology were corroborated by conducting experiments. Results A total of 17,204 TNBC targets were screened, and 301 potential targets of nomilin were identified. Through the PPI network, eight core targets of nomilin against TNBC were pinpointed, namely BCL2, Caspase3, CyclinD1, EGFR, HSP90AA1, KRAS, PARP1, and TNF. Molecular docking, molecular dynamics simulation and proteome microarray revealed that nomilin exhibits strong binding activity to these core proteins. Enrichment analysis results indicated that the anti-TNBC effect of nomilin is associated with PI3K/Akt pathway. In vitro and in vivo experiments have demonstrated that nomilin inhibits TNBC cell proliferation and migration while promoting cell apoptosis through the PI3K/Akt pathway. Conclusion For the first time, the research effectively discovered the objectives and mechanisms of nomilin in combating TNBC using network pharmacology, molecular docking, molecular dynamics simulation, proteome microarray and experimental confirmation, presenting a hopeful approach for treating TNBC. Graphical Abstracthttps://doi.org/10.1186/s10020-024-00928-2Network pharmacologyMolecular dockingNomilinTriple negative breast cancerPI3K/Akt pathway |
| spellingShingle | Zhixuan Wu Haoyi Xiang Xiaowu Wang Rongrong Zhang Yangyang Guo Liangchen Qu Jingyao Zhou Yanyi Xiao Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer Molecular Medicine Network pharmacology Molecular docking Nomilin Triple negative breast cancer PI3K/Akt pathway |
| title | Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer |
| title_full | Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer |
| title_fullStr | Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer |
| title_full_unstemmed | Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer |
| title_short | Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer |
| title_sort | integrating network pharmacology molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple negative breast cancer |
| topic | Network pharmacology Molecular docking Nomilin Triple negative breast cancer PI3K/Akt pathway |
| url | https://doi.org/10.1186/s10020-024-00928-2 |
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