Evaluation of the anticancer effects of ellagic acid and cisplatin in cisplatin-sensitive and -resistant MDA-MB-231 breast cancer cells

Ellagic acid (EA) is a natural polyphenol noted for its antiproliferative and pro-apoptotic effects. This study investigates the impact of EA, alone or combined with cisplatin (CIS), on the expression of angiogenesis, apoptosis, metastasis, and chemoresistance-related genes and proteins in cisplatin-sensitive and -resistant MDA-MB-231 breast cancer cells. Cell viability was evaluated by cytotoxicity assay, while gene and protein expression levels were analyzed via qPCR and immunocytochemistry. Molecular docking was used to assess EA's binding affinity to target proteins. The IC₅₀ values of EA and CIS were 29 µM and 38.2 µM in cisplatin-sensitive MDA-MB-231 cells, and 49.5 µM and 80.2 µM in cisplatin-resistant cells, respectively. In both cell types, EA significantly decreased the expression of the ABCB1 and VEGF genes, especially at 24 and 48 h. EA alone and combined with CIS suppressed MMP2 and MMP9 expression across both cell types. Additionally, EA and CIS + EA treatments suppressed Bcl-2 expression and upregulated Bax expression. Immunocytochemical results aligned with gene expression data, demonstrating reduced protein levels. Molecular docking demonstrated strong binding of EA to Bax and MMP9. These results indicate that EA exerts notable anticancer activity by targeting genes associated with drug resistance, angiogenesis, apoptosis, and metastasis. The findings highlight EA's therapeutic potential in breast cancer treatment, alone or with CIS. Further detailed in vivo and clinical studies are needed to confirm these promising results.