Abstract
Breast 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.
Key words
cancer - anticancer drugs - cancer pharmacology - drug research - pharmacology
