Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway

Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ER alpha-SRC1 coactivator activity and expression of specific ER alpha-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17 beta-oestradiol and mimosine at the ER alpha ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson-Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 mu M with significant cell proliferation (120.5%) compared to 17 beta-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 mu M showed the highest ER alpha binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 mu M) and PGR (13.9-fold at 0.01 mu M) genes. ER alpha-mimosine binding energy was -49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ER alpha-LBD. The results suggested that mimosine has oestrogenic activity.