In Silico Prediction of Mechanism of Erysolin-induced Apoptosis in Human Breast Cancer Cell Lines

Targeted therapy has been gaining momentum to be a promising strategy for drug development research. Natural compounds and their synthetic analogues have provided several promising anticancer drugs. Erysolin present in the Eruca sativa better known as rocket plant has been scarcely studied. In the present study, we assessed the anticancer potential and underlying mechanism(s) of action of erysolin in human breast cancer cell lines (MCF-7 and MDA-MB-231) using the in vitro and/or in silico experiments. Incubation of these cell lines with erysolin (10 and 50 μM) for 72 h resulted in 50-70% apoptosis in both cell lines at 50 μM with concomitant decrease in the cell viability. However, 10 μM erysolin induced 20% apoptosis in MDA-MB-231 cells while it was unresponsive in the MCF-7 cells. Further, our in silico results revealed significant interaction and better inhibition of erysolin to CDK2, CDK6, Bcl2 and ER-α compared to the standard reference compounds. Moreover, erysolin also showed higher affinity against interface of p53-MDM2 which might stimulate p53 in tumor cells or induces restoration of mutant p53 thereby making these cancer cells to undergo apoptosis. Feeble interactions with pro-apoptotic protein BAX, caspases 3 and 8 also indicate possible involvement of extrinsic pathway in the erysolin-mediated apoptosis. The results showed that erysolin is a promising natural anticancer and anti-estrogenic agent. Further, the in silico protocol for elucidating and validating apoptosis mechanism(s) by unknown compounds could also be used.