Dietary Estrogens Act through Estrogen Receptor-Mediated Processes and Show No Antiestrogenicity in Cultured Breast Cancer Cells.

Abstract

Dietary estrogens are believed to exert their estrogenic or antiestrogenic (chemopreventive) action in estrogen responsive cells by interacting with the estrogen receptor (ER). The present study was undertaken to evaluate a direct role of ER in estrogenic or antiestrogenic activities of three dietary estrogens (coumestrol, genistein and zearalenone). HeLa cells were transiently co-transfected with an expression vector for ER and an estrogen-responsive reporter gene construct. Coumestrol, genistein, and zearalenone all increased the activity of the reporter gene, only in the presence of the ER, and the activation was blocked with the ER antagonist ICI 164,384, demonstrating an ER-specific, agonist response. In addition, in MCF-7 cells, coumestrol and zearalenone increased the expression of the estrogen-responsive pS2 gene. Coumestrol and genistein inhibited the purified estrogen-specific 17ß-hydroxysteroid oxidoreductase enzyme and the conversion of estrone to 17ß-estradiol in T-47D cells, which contain this enzyme. However, they did not inhibit the estrone-induced proliferation of T-47D cells. In conclusion, coumestrol, genistein, and zearalenone are all potent estrogens in vitro, and they act through ER mediated mechanism. Our findings give no evidence to support the idea that these compounds act as antiestrogens through competition for the binding sites of ER or by inhibition of the conversion of estrone to 17ß-estradiol in breast cancer cells, since this effect was nullified by their agonist action on cell proliferation. Therefore, their suggested chemopreventive action in estrogen-related cancers must be mediated through other mechanisms.ImagesFigure 2. AFigure 2. BFigure 2. CFigure 2. DFigure 2. EFigure 3. AFigure 3. BFigure 4. AFigure 4. BFigure 4. CFigure 4. DFigure 4. EFigure 5.Figure 6.Figure 7.Figure 8.Figure 9. AFigure 9. BFigure 9. C

Dietary Estrogens Stimulate Human Breast Cells to Enter the Cell Cycle

“…3, or DDT (8)(9)(10)(11) (18,19). However, genistein at lower concentrations has also been shown to increase the growth of ER-positive cells (19,20).…”

Anticancer activity of genistein on implanted tumor of human SG7901 cells in nude mice

“…Genistein is a planar molecule with an aromatic A-ring, has a second oxygen atom from that in the A ring, and has a molecular mass similar to those of the steroidal estrogens. It has estrogenic properties in receptor binding assays [15,16] , cell culture [17,18] , and uterine weight assays [19][20][21] . Genistein inhibits topoisomerase Ⅱ [33] , platelet-activating factor-and epidermal growth factorinduced expression of c-fos [34] , diacylglycerol synthesis [35] , and tyrosine kinases [36] .…”

“…Genistein has estrogenic properties in receptor binding assays [15,16] , cell culture [17,18] , and uterine weight assays [19][20][21] . Genistein inhibits microsomal lipid peroxidation [22] and angiogenesis [23] .…”

Health potential of soy isoflavones for menopausal women

“…Potential cancer risk associated with phyto-oestrogens Some recent in vitro and in vivo studies suggest that the growth of normal and neoplastic breast epithelium is promoted by phyto-oestrogens 70,92,93 . The widely used MCF-7 breast cancer cell line responds with proliferation to doses of genistein in the low micromolar range both in vitro and in vivo 70 .…”