Simvastatin Mediated Suppression of Epithelial-Mesenchymal Transition: A Potential Therapeutic Strategy for Breast Cancer

Background Repurposing of a hydroxylmethylglutaryl coenzyme A reductase inhibitor like simvastatin has gained significant interest in oncologic treatment owing to the pleiotropic effects. However, the role of simvastatin in inhibiting epithelial-mesenchymal transition (EMT), a critical process in cancer metastasis, remains underexplored. Purpose To investigate the anti-EMT potential of simvastatin in human breast cancer MCF-7 cells. Materials and Methods MCF-7 cells were treated with simvastatin, and the anti-proliferative and pro-apoptotic effect were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescence double staining method, respectively. Cell migration and cell aggregation assays were carried out to determine EMT-associated activities. A key regulator of EMT, β-catenin activity was measured using an indirect enzyme-linked immunosorbent assay, and the gene expression in response to simvastatin treatment was analyzed by reverse transcriptase polymerase chain reaction. Results A dose-dependent cytotoxic activity was induced by simvastatin in MCF-7 cells, associated with morphological alterations indicative of apoptosis. Enhanced apoptotic cell death on simvastatin administration was validated by fluorescence nuclear staining. A marked reduction in migratory capacity and cell aggregation was observed in simvastatin-treated cells. Activity of β-catenin and the messenger ribonucleic acid expression were found to be downregulated. Conclusion Simvastatin effectively suppressed EMT-related processes in MCF-7 breast cancer cells by inhibiting cell proliferation, migration, aggregation, and β-catenin expression. These findings highlight the potential of simvastatin as a therapeutic agent for preventing breast cancer metastasis through EMT inhibition.