A preliminary study to identify existing drugs for potential repurposing in breast cancer based on side effect profile

Abstract

AbstractBreast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women after lung cancer. The present study aims to identify potential drug candidates using the PROMISCUOUS database for breast cancer based on side effect profile and then proceed with in silico and in vitro studies. PROMISCUOUS database was used to construct a group of drugs that share maximum side effects with letrozole. Based on the existing literature, ropinirole, risperidone, pregabalin, and gabapentin were selected for in silico and in vitro studies. The molecular docking was carried out using AUTODOCK 4.2.6. MCF-7 cell line was used to evaluate the anti-cancer activity of the selected drugs. PROMISCUOUS database revealed that as many as 23 existing drugs shared between 62 and 79 side-effects with letrozole. From docking result, we found that, ropinirole showed a good binding affinity (−7.7 kcal/mol) against aromatase compared to letrozole (−7.1 kcal/mol) which was followed by gabapentin (−6.4 kcal/mol), pregabalin (−5.7 kcal/mol) and risperidone (−5.1 kcal/mol). From the in vitro results, ropinirole and risperidone showed good anti-cancer activity of IC50 with 40.85±11.02 μg/ml and 43.10±9.58 μg/ml cell viability. Based on this study results and existing literature we conclude that risperidone, pregabalin, and gabapentin are not ideal candidates for repurposing in breast cancer but ropinirole could be an excellent choice for repurposing in breast cancer after further studies.