One of the 5-aminosalicylates drug, mesalamine as a drug repurposing lead against breast cancer

Abstract

Abstract Background Breast cancer is the world's second leading cause of death in women. The problem of chemoresistance in breast cancer is proving to be a challenge for researchers and several oncologists all around the world. Current treatment modalities are associated with severe toxicities and lower efficiency. Hence, there is an unmet need for the development of novel drugs that can be used as adjuvants in breast chemotherapy. One of the strategies used to overcome this problem and that has received scientific coverage over the years is ‘Drug Repurposing’. For this purpose, a list of 5-aminosalicylates drugs were evaluated for their drug repurposing potential in breast cancer. Mesalamine, sulfasalazine, balsalazide, and olsalazine were docked with high expression signatures in cancer cells such as EGFR (epidermal growth factor receptor), ERα (Estrogen Receptor alpha), Aromatase, mTOR (mammalian target of rapamycin), ALOX5 (Arachidonate 5-lipoxygenase), and Topoisomerase II. Results Docking analysis revealed that the selected ligands (drug) exhibited good binding affinity for all receptors. Based on the specificity with receptors, mesalamine was further selected for in vitro functional validation in a breast cancer cell line. Cell-based cytotoxicity assay in MCF-7 (Michigan Cancer Foundation-7) cells demonstrated the anticancer potential of mesalamine in breast cancer with IC-50 (Inhibitory Concentration) of 6.358 µM. Conclusions Significant morphological alterations were observed in breast cells treated with mesalamine. Further studies are warranted to explore the anticancer effect of mesalamine in breast cancer and its role in combination therapies to be used as an adjuvant in chemotherapy.

Keywords

• Drug repurposing
• Breast cancer
• 5-Aminosalicylates
• MCF-7
• Chemoresistance
• Mesalamine