RESUMO
Breast cancer is the leading cause of cancer-related death in women worldwide, and despite multiple chemotherapeutic approaches, effective treatment strategies for advanced metastatic breast cancer are still lacking. Metabolic reprogramming is essential for tumor cell growth and propagation, and most cancers, including breast cancer, are accompanied by abnormalities in energy metabolism. Here, we confirmed that sodium cantharidate inhibited cell viability using the Cell Counting Kit-8, clonogenic assay, and Transwell assay. The cell cycle and apoptosis assays indicated that sodium cantharidate induced apoptosis and cell cycle arrest in breast cancer cells. Additionally, proteomic assays, western blots, and metabolic assays revealed that sodium cantharidate converted the metabolic phenotype of breast cancer cells from glycolysis to oxidative phosphorylation. Furthermore, bioinformatics analysis identified possible roles for p53 with respect to the effects of sodium cantharidate on breast cancer cells. Western blot, docking, and phosphatase assays revealed that the regulation of p53 activity by sodium cantharidate was related to its inhibition of protein phosphatase 5 activity. Moreover, sodium cantharidate significantly inhibited tumor growth in tumor-bearing nude mice. In summary, our study provides evidence for the use of sodium cantharidate as an effective and new therapeutic candidate for the treatment of human breast cancer in clinical trials.
