Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of Cannabis sativa in Breast Cancer.

BACKGROUND

Breast Cancer (BC), a common fatal disease and the deadliest cancer next to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy is marked by targeting the activities of some receptors such as Estrogen Receptor alpha (ER-α). At present, one of the most commonly used and approved marketed therapeutic drugs for BC is tamoxifen. Despite the short-term success of tamoxifen usage, its long time treatment has been associated with significant side effects. Therefore, there is a pressing need for the development of novel anti-estrogens for the prevention and treatment of BC.

OBJECTIVE

In this study, we evaluate the inhibitory effect of Cannabis sativa phytoconstituents on ER-α.

METHODS

Glide and induced fit docking followed by ADME, automated QSAR and binding free energy (Δ) studies were used to evaluate anti-breast cancer and ER-α inhibitory activity of Cannabis sativa, which has been reported to be effective in inhibiting breast cancer cell proliferation.

RESULTS

Phyto-constituents of Cannabis sativa possess lower docking scores and good Δ when compared to that of tamoxifen. ADME and AutoQSAR studies revealed that our lead compounds demonstrated the properties required to make them promising therapeutic agents.

CONCLUSION

The results of this study suggest that naringenin, dihydroresveratrol, baicalein, apigenin and cannabitriol could have relatively better inhibitory activity than tamoxifen and could be a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo and/or in vitro assays could be conducted to verify the ability of these compounds.