Ribitoborate Synergism with Histone Deacetylase Inhibitor Romidepsin as a Potential Treatment for Breast Cancer

Triple-negative breast cancer (TNBC) is a subtype associated with poor prognosis and low survival rates, largely due to limited treatment options. In recent years, histone deacetylase (HDAC) inhibitors have emerged as promising anti-cancer candidates due to their attractive epigenetic properties and distinct mechanisms of action but have shown limited success in solid tumors. Here, we explore ribitoborate along with HDAC inhibitors for potential use as a treatment for TNBC. Experiments were performed on the TNBC cell line MDA-MB-231. The results of the study revealed that ribitoborate and romidepsin showed synergistic responses leading to significant arrest of cell proliferation (80%) (p < 0.01) as well as migration inhibition. These effects were associated with downregulation of c-Myc, survivin, Bcl-2, and cyclin D1, as well as upregulation of p53 and p21 proteins; notably the changes were significantly greater with the combined treatment than with either ribitoborate or romidepsin alone. Romidepsin and ribitoborate combined treatment time-dependently increased cell death of MDA-MB-231 cells with greater efficiency than romidepsin alone. Cell death by apoptosis was supported by the upregulation of H3k9 and H3k27 acetylation with decreasing proliferation. These results suggest the great potential of the drug combination for treatment of TNBC. The underlying molecular mechanisms for synergy could be further explored for potential development of new combined therapy for breast cancer.