J Contemp Dent Pract. 2025 Nov 1;26(11):1050-1059. doi: 10.5005/jp-journals-10024-3971.
ABSTRACT
AIM: This study aims to examine the pro-apoptotic and anti-migratory effects of Berberine in KB-1 oral cancer cells and its role in ferroptosis via glutathione peroxidase4/six-transmembrane epithelial antigen of prostate3 (GPX4/STEAP3) signaling pathway.
MATERIALS AND METHODS: KB-1 cells were treated with Berberine, and cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes were analyzed via phase-contrast microscopy, while nuclear fragmentation was examined using acridine orange/ethidium bromide (AO/EtBr) staining. Molecular docking, gene expression analyses were performed to assess ferroptosis markers. Wound healing and migration assays evaluated Berberine’s effect on cell migration.
RESULTS: Berberine reduced cell viability (IC50: 22.2 μM) and induced morphological changes, including shrinkage and membrane blebbing. AO/EtBr staining confirmed nuclear fragmentation. Gene expression analysis showed ferroportin upregulation and GPX4, STEAP3, and transferrin receptor 1 (TFR1) downregulation, validated by western blotting. Molecular docking confirmed strong Berberine binding, particularly with GPX4 and STEAP3. Wound healing and migration assays showed significant migration suppression. All experimental data were statistically evaluated using the Student’s t-test and one-way ANOVA.
CONCLUSION: Berberine induces ferroptosis and inhibits KB-1 oral cancer cell proliferation and migration by modulating the ferroptosis signaling pathway, suggesting its potential as a novel therapeutic agent.
CLINICAL SIGNIFICANCE: By promoting iron-dependent cell death and suppressing migratory capacity, Berberine may overcome resistance to conventional therapies and reduce metastatic progression. Its natural origin and prior safety profile support drug repurposing opportunities, though challenges such as poor bioavailability and systemic toxicity must be addressed. These findings provide a foundation for biomarker-driven preclinical and early clinical evaluations. How to cite this article: Alassiri S. Berberine Induces Ferroptosis and Impairs Migration via Glutathione Peroxidase4/Six-transmembrane Epithelial Antigen of Prostate3 Signaling Pathway in Oral Cancer Cells. J Contemp Dent Pract 2025;26(11):1050-1059.
PMID:41368744 | DOI:10.5005/jp-journals-10024-3971
