Unveiling the inhibitory effects of tannic acid and doxorubicin combination on pyruvate kinase M2 in breast cancer cells.

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer deaths among women worldwide. This study investigates the combined effects of tannic acid (TA) and doxorubicin (DOX) on glucose metabolism in estrogen receptor-positive (MCF7) and triple-negative (MDA-MB-231) BC cells by targeting pyruvate kinase M2 (PKM2). Cells were treated with TA, DOX, and their combinations, then analyzed for cytotoxicity, apoptosis, cell cycle progression, migration, and colony formation. PKM2 expression levels and activity were also measured. Results demonstrated that TA, alone and with DOX, effectively induced apoptosis and inhibited migration and colony formation in both cell lines. Notably, PKM2 mRNA expression was significantly reduced, particularly in TA-treated groups. Furthermore, glucose levels in the medium increased significantly following TA treatment, indicating reduced glucose uptake by cancer cells, and indicating that combining TA with DOX can disrupt glucose metabolism and diminish aggressive behaviors in BC cells. By targeting the glycolytic enzyme PKM2, TA lowers its expression, restricts glucose uptake, and enhances chemotherapy-driven apoptosis while limiting migration and colony formation. These findings underscore the potential of metabolic reprogramming through combining TA with DOX as a promising therapeutic strategy to improve BC treatment outcomes.