Study On The Inhibiting Effects Of Equol On MCF-7Cells Proliferation And Its Molecular Mechanisms

Objective To investigate the proliferation inhibition effects of equol on human breast cancer cell line MCF-7and explore its molecular mechanisms.Method MCF-7and MCF-10A cells were treated with10"9M estradiol and different concentration of equol, ranging from10-7M to10-5M. After the treatment, morphological changes of apoptosis were observed with microscope. The numbers and proliferation rate of cells were examined by MTT method and the cell apoptosis percentage and cell cycle phase were determined by flow cytometry. The ability of cell migration were measured by wound healing assay. At last, the expressions of bag-1, bcl-2, VEGF, ERK1/2, p-ERK1/2, p38and p-p38protein ere determined using Western blotting. We understood the underlying mechanism of the inhibiting effect of equol on MCF-7cells proliferation.Result The estradiol promoted the proliferation of MCF-7cells. A dose and time effect of proliferation inhibition of equol was proved in MCF-7. Equol had no obvious effect on MCF-10A cells.Compared with the control group, the MCF-7cell apoptosis percentage increased significantly in the groups of equol, and the cell cycle arrest in G0G1phase. The ability of cell migration decreased with the increase of equol concentration.The expression of bag-1, bcl-2and VEGF were increased by the estradiol with while the equol could decrease it, and the inhibition were distinct along with the increase of equol concentration. The expression of bag-1, bcl-2and VEGF were at the lowest level after being treated with10-5M of equol.The expression of ERK1/2and p38protein had no obviously change neither in the estradiol group nor in the equol groups. The estradiol could increase the expression of p-ERK1/2and p-p38protein, while the equol could decrease it. The expression of p-ERK1/2and p-p38protein were decreased gradually with the increase concentration of equol. Conclusion The equol could inhibit the proliferation of the breast cancer cell lines MCF-7and had a dose and time effect trend in10-7M-10-5M. Its inhibitory effect may be due to inducing apoptosis, arresting the cell cycle in G0G1phase, down-regulating the expression of bag-1, bcl-2and VEGF, p-ERK1/2and p-p38protein. The results suggest that the equol may prevent and serve as supplementary therapy on the breast cancer with positive estrogen receptor.