Phytoestrogens induce differential effects on both normal and malignant human breast cells in vitro

To explore the effect and pathway of phytoestrogens in vitro on the growth of both normal and malignant breast cells.

Normal breast MCF-10A cells and breast cancer MCF-7 cells were incubated with 10 (-10)-10(-4)  mol/l genistein, resveratrol, and quercetin (plasma concentrations in human: 10 nmol/l-10 μmol/l) for 48 h and were then extracted for a cell proliferation assay (MTT), and for a cell death assay (TUNEL) assay. The proteins involved in the proliferative and apoptotic pathways were evaluated by Western blot analysis. Additionally, a comparison with 17β-estradiol as well as an evaluation of the differential effects on estrogen receptors (ER) α and β were performed.

MCF-7 cell proliferation was significantly inhibited at the concentrations greater than 10(-4) mol/l for all three phytoestrogens and from 10 (-5) mol/l for resveratrol and quercetin. MCF-10A cell proliferation was significantly increased at the concentrations from 10 (-8) to 10 (-5) mol/l for genistein and resveratrol and only at 10 (-5) mol/l for quercetin. Apoptotic cells were significantly increased by these phytoestrogens in the MCF-7 cells. At a concentration of 10 (-7)  mol/l of these phytoestrogens, a significant reduction of PI3K and Akt and an increase of Fas ligand, Fas-associated protein with death domain, cytochrome C, truncated Bid, caspase-9, and caspase-3 were noted in the MCF-7; PI3K and Akt were significantly increased in the MCF-10A. ERβ expression was significantly elevated in MCF-10A and MCF-7 with these phytoestrogens. The effects of estradiol on normal and malignant breast cells were completely opposite to those of phytoestrogens.

This study demonstrates that phytoestrogens have antiproliferative effects on breast cancer cells via an ER-dependent mechanism, even at low concentrations, but are also capable of maintaining the survival of normal breast cell via ER-independent or other mechanisms.