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Anticancer drug resistance is one of the biggest hurdles in the treatment of breast cancer. Drug repurposing is a viable option fordeveloping novel medical treatment strategies since this method is more cost-efficient and rapid. Antihypertensive medicines have recently been found to have pharmacological features that could be used to treat cancer, making them effective candidates for therapeutic repurposing. The goal of our research is to find a potent antihypertensive drug that can be repurposed as adjuvant therapy for breast cancer. In this study, virtual screening was performed using a set of Food and Drug Administration (FDA)-approved antihypertensive drugs as ligands with selected receptor proteins (EGFR, KRAS, P53, AGTR1, AGTR2, and ACE) assuming these proteins are regarded to have a significant role in hypertension as well as breast cancer. Further, our in-silico results were further confirmed by an in-vitro experiment (cytotoxicity assay). All the compounds (enalapril, atenolol, acebutolol, propranolol, amlodipine, verapamil, doxazosin, prazosin, hydralazine, irbesartan, telmisartan, candesartan, and aliskiren) showed remarkable affinity towards the target receptor proteins. However, maximum affinity was displayed by telmisartan. Cell-based cytotoxicity study of telmisartan in MCF7 (breast cancer cell line) confirmed the anticancer effect of telmisartan. IC50 of the drug was calculated to be 7.75 µM and at this concentration, remarkable morphological alterations were observed in the MCF7 cells confirming its cytotoxicity in breast cancer cells. Based on both in-silico and in-vitro studies, we can conclude that telmisartan appears to be a promising drug repurposing candidate for the therapeutic treatment of breast cancer.

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.