Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation

Objective: Berberine (BBR) has garnered attention for its potential effectiveness against triple-negative breast cancer (TNBC). To further understand its pharmacological mechanisms, this study employed a combination of network pharmacology analysis and experimental verification for providing insight...

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Main Authors: Tian Qin, Kaixuan Liu, Yushi Yang, Jinjin Huang, Tengxiang Chen, Yinhui Jiang, Shu Xu
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Phytomedicine Plus
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667031324001684
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author Tian Qin
Kaixuan Liu
Yushi Yang
Jinjin Huang
Tengxiang Chen
Yinhui Jiang
Shu Xu
author_facet Tian Qin
Kaixuan Liu
Yushi Yang
Jinjin Huang
Tengxiang Chen
Yinhui Jiang
Shu Xu
author_sort Tian Qin
collection DOAJ
description Objective: Berberine (BBR) has garnered attention for its potential effectiveness against triple-negative breast cancer (TNBC). To further understand its pharmacological mechanisms, this study employed a combination of network pharmacology analysis and experimental verification for providing insights into the potential of BBR as a therapeutic option for TNBC. Methods: Through an application of network pharmacology methods to foresee the essential targets and pathways of BBR in countering TNBC, an analysis of the protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out. The confirmation of the bond between BBR and the target sites occurred via molecular docking utilizing CavityPlus and Autodock vina. To validate the outcomes of the network pharmacology analysis, experimental verification was performed through in vitro experiments. Results: By searching the overlap between BBR and TNBC targets, a total of 257 potential targets were retrieved. PPI network analysis revealed that top of 15 targets as the pivotal gene. In the analysis of gene ontology (GO) enrichment results of effective target GO functional enrichment analysis suggested that BBR may be involved in protein phosphorylation and anti-apoptotic biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the anti-cancer effect of BBR was mediated by multiple pathways, such as pathways in cancer signaling pathways and apoptosis signaling pathways. The ''Compound-target-GO-pathway-disease'' network constructed and acetylation targets with molecular docking demonstrated the regulation of acetylation by BBR. Subsequently, in vitro assay results indicated that BBR, as an inhibitor of deacetyltransferase (KDACi), was capable of inhibiting the proliferation and migration of MDA-MB-231 cells and inducing cell apoptosis. Conclusion: Through combining network pharmacology with vitro validation, this study identified BBR as a potential target of KDACi in TNBC, providing new insights into the pharmacology of acetylation in the treatment of TNBC.
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spelling doaj-art-d8bdb04df0ff4e4487bd5005460e08c32025-08-21T04:17:21ZengElsevierPhytomedicine Plus2667-03132025-08-015310069410.1016/j.phyplu.2024.100694Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validationTian Qin0Kaixuan Liu1Yushi Yang2Jinjin Huang3Tengxiang Chen4Yinhui Jiang5Shu Xu6College of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550009, ChinaCollege of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550009, ChinaAffiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, ChinaAffiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, ChinaDepartment of Physiology, Guizhou Medical University, Guiyang, Guizhou 550009, ChinaKey Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, Guizhou 550009, ChinaCollege of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550009, China; Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, China; Corresponding author at: Department of Pathology, College of Clinical Medicine, Guizhou Medical University, No.9 Beijing Lu, Guiyang, Guizhou 550009, China.Objective: Berberine (BBR) has garnered attention for its potential effectiveness against triple-negative breast cancer (TNBC). To further understand its pharmacological mechanisms, this study employed a combination of network pharmacology analysis and experimental verification for providing insights into the potential of BBR as a therapeutic option for TNBC. Methods: Through an application of network pharmacology methods to foresee the essential targets and pathways of BBR in countering TNBC, an analysis of the protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out. The confirmation of the bond between BBR and the target sites occurred via molecular docking utilizing CavityPlus and Autodock vina. To validate the outcomes of the network pharmacology analysis, experimental verification was performed through in vitro experiments. Results: By searching the overlap between BBR and TNBC targets, a total of 257 potential targets were retrieved. PPI network analysis revealed that top of 15 targets as the pivotal gene. In the analysis of gene ontology (GO) enrichment results of effective target GO functional enrichment analysis suggested that BBR may be involved in protein phosphorylation and anti-apoptotic biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the anti-cancer effect of BBR was mediated by multiple pathways, such as pathways in cancer signaling pathways and apoptosis signaling pathways. The ''Compound-target-GO-pathway-disease'' network constructed and acetylation targets with molecular docking demonstrated the regulation of acetylation by BBR. Subsequently, in vitro assay results indicated that BBR, as an inhibitor of deacetyltransferase (KDACi), was capable of inhibiting the proliferation and migration of MDA-MB-231 cells and inducing cell apoptosis. Conclusion: Through combining network pharmacology with vitro validation, this study identified BBR as a potential target of KDACi in TNBC, providing new insights into the pharmacology of acetylation in the treatment of TNBC.http://www.sciencedirect.com/science/article/pii/S2667031324001684Triple-negative breast cancerBerberineNetwork pharmacologyKDACIExperimental verification
spellingShingle Tian Qin
Kaixuan Liu
Yushi Yang
Jinjin Huang
Tengxiang Chen
Yinhui Jiang
Shu Xu
Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation
Phytomedicine Plus
Triple-negative breast cancer
Berberine
Network pharmacology
KDACI
Experimental verification
title Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation
title_full Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation
title_fullStr Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation
title_full_unstemmed Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation
title_short Pharmacological mechanisms of berberine against triple negative breast cancer: Integration of network pharmacology and experimental validation
title_sort pharmacological mechanisms of berberine against triple negative breast cancer integration of network pharmacology and experimental validation
topic Triple-negative breast cancer
Berberine
Network pharmacology
KDACI
Experimental verification
url http://www.sciencedirect.com/science/article/pii/S2667031324001684
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