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This study assessed the therapeutic effects of BRB on cell proliferation, cell\u2010cycle progression, apoptosis, and metastasis in human (MDA\u2010MB\u2010231) and murine (4T1) triple\u2010negative breast cancer cells. Cytotoxicity testing using a crystal violet assay showed IC\u2085\u2080 values of 40\u2009\u00b5M for MDA\u2010MB\u2010231 and 10\u2009\u00b5M for 4T1 after 48\u2009h of treatment. BRB induced S\u2010phase arrest in MDA\u2010MB\u2010231 and G2\/M\u2010phase arrest in 4T1 cells. It also induced late apoptosis in both cell lines, along with increased reactive oxygen species production and loss of mitochondrial membrane potential. Furthermore, BRB exhibited marked anti\u2010metastatic potential by inhibiting cell adhesion, migration, and invasion. Scratch\u2010wound and Transwell assays demonstrated a significant, concentration\u2010dependent reduction in migratory capacity, while 3D spheroid assays confirmed strong suppression of invasive behavior. BRB also reduced adhesion to extracellular matrix components, particularly collagen IV. At the molecular level, BRB significantly downregulated MMP2 and MMP9 mRNA expression in both cell lines, supporting its role in inhibiting extracellular matrix remodeling and metastatic progression. Molecular docking simulations indicated that BRB has a favorable binding energy with multiple cancer\u2010related targets, including MDM2\u2010P53, BCL2, Caspases (3, 8, and 9), MCL1 complexes, and matrix metalloproteinases (MMP\u20102 and MMP\u20109). The compound maintained stable hydrogen bonds, \u03c0\u03c0\u2010stacking interactions, and hydrophobic contacts, often achieving higher docking scores than the co\u2010crystallized ligand. Overall, the results suggest that BRB exerts multi\u2010targeted anticancer effects by regulating processes such as proliferation, apoptosis, migration, and adhesion, indicating that BRB could be a promising candidate for breast cancer therapy.<\/jats:p>","DOI":"10.1002\/cbin.70165","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:48:08Z","timestamp":1779194888000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Berberine Chloride Induces Apoptosis and Inhibits Adhesion, Migration, and Invasion in MDA\u2010MB\u2010231 and 4T1 Breast Cancer Cells: An Integrative In Vitro and In Silico Study"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4918-9129","authenticated-orcid":false,"given":"Abir","family":"Salek","sequence":"first","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7404-2404","authenticated-orcid":false,"given":"Mouna","family":"Selmi","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-248X","authenticated-orcid":false,"given":"Aida","family":"Lahmer","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabrouk","family":"Horchani","sequence":"additional","affiliation":[{"name":"Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11ES39), Medicinal Chemistry and Natural Products, Faculty of Sciences of Monastir University of Monastir, Avenue of Environment Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Maatouk","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahassen","family":"Barboura","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifa","family":"Messai","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihed","family":"Boubabaker","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"},{"name":"Faculty of Pharmacy of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hichem Ben","family":"Jannet","sequence":"additional","affiliation":[{"name":"Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11ES39), Medicinal Chemistry and Natural Products, Faculty of Sciences of Monastir University of Monastir, Avenue of Environment Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Chekir\u2010Ghedira","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Bouhlel\u2010Chatti","sequence":"additional","affiliation":[{"name":"Research Laboratory of Bioactive Natural Products and Biotechnology LR24ES14, Faculty of Dental Medicine of Monastir University of Monastir Monastir Tunisia"},{"name":"Department of Biology and Geology, Higher Institute of Applied Science and Technology of Gabes University of Gabes Gabes Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Addressing the Preventive and Therapeutic Perspective of Berberine Against Diabetes: Heliyon [Internet]. 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