The Impact of Simultaneous Epigenetic and Epitranscriptomic Intervention in Breast Cancer Cells

Aim: Breast cancer remains a significant cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Epigenetic and epitranscriptomic regulation have emerged as promising avenues for novel treatments. Sodium Butyrate (NaB) and Meclofenamic Acid (MFA) have gained attention for their respective roles in epigenetic and epitranscriptomic modulation. NaB, a histone deacetylase inhibitor, serves as a critical regulator of chromatin remodeling and gene expression. MFA has been identified to be a potent inhibitor of the FTO enzyme. This inhibitory potential marks its role in epitranscriptomic regulation. This study aimed to investigate the potential effects of MFA and NaB, individually and in combination, on the MCF7 breast cancer cell line. Method: In order to investigate the cytotoxic and apoptotic effects of the combination treatment of MFA and NaB, cell viability assay, Annexin V analysis and Acridine Orange/DAPI staining were executed. Results: The results revealed that the combination treatment unexpectedly exhibited antagonistic effects. This was evidenced by a remarkable increase in cell viability and a decreased apoptotic response compared to individual treatments. The strongest antagonistic effect was observed when the cells were treated with 100 μM MFA and 2 mM NaB for a period of 48 hours (CI = 88.3). Conclusion: This study, for the first time, sheds light on the complex interaction between meclofenamic acid and sodium butyrate that reveals an unexpected antagonistic effect on MCF7 breast cancer cells. These findings challenge conventional concepts of synergistic interactions and underscore the complexity of drug combinations in breast cancer treatment.