Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture.

Abstract

We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods, herbs, and spices and in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans. Results show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked differences in their ability to induce end products of estrogen action and to regulate cell proliferation. All of the different classes of estrogens stimulated cell proliferation at concentrations that half-saturated ER, but only some classes were able to induce estrogen-regulated end products. Genistein, a common phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its effects on cell proliferation and ability to induce estrogen-regulated end products. Moreover, we found that many of the foods, herbs, and spices commonly consumed by humans contain significant amounts of phytoestrogens, and consumption of soy milk, a phytoestrogen-rich food, markedly increases the levels of phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet high in phytoestrogens would significantly reduce the binding of weak xenoestrogens to ER in target tissues in vivo. Environ Health Perspect 1 05(Suppl 3): 637-645 (1997)

Antiosteoporotic compounds from seeds of Cuscuta chinensis

“…It has been shown that ERK induces the AP-1 activation (Karin, 1995), thus kaempferol may promote the ALP activity in UMR-106 cells through similar mechanism. In the presence of ER, kaempferol activated AP-1 more potently than quercetin, which well resembles other finding that kaempferol antagonizes estradiol more potently than quercetin (Zava et al, 1997;Harris et al, 2005). Interestingly, isorhamnetin exhibited inhibitory effect on AP-1 activation in the presence of ER subtypes, suggesting its action may be different with quercetin or kaempferol.…”

“…Quercetin and kaempferol activated AP-1 reporter by both ER␣ and ER␤, which makes them behave more like ER antagonists. This further demonstrated previous observation that kaempferol and quercetin antagonized 17␤-estradiol, and kaempferol was more potent than quercetin (Zava et al, 1997;Harris et al, 2005). Contrary to quercetin and kaempferol, isorhamnetin (10-50 M) inhibited AP-1 reporter expression in the presence of ER␣ or ER␤.…”

Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study

“…This result is consistent with the results of the pooled analysis of prospective studies where the OR for women in the top quintile of oestradiol was 2.00 (95% CI ¼ 1.47 -2.71) and for women in the top quintiles of oestradiol and oestrone were 2.19 (95% CI ¼ 1.48 -3.22), respectively (TEHBCCG, 2002). As oestradiol has greater potency and binds with oestrogen receptor-a with greater affinity than oestrone (Zava et al, 1997), a stronger association of risk with oestradiol than with oestrone is usually expected. Measurement error is not likely to be responsible for our Controlling for matching factors only.…”

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

“…Among the agents tested, genistein showed more prominent suppression of the expression of VEGF mRNA and bFGF mRNA. Genistein, an isoflavone in soybeans, was originally recognised as a weak oestrogen and also an oestrogen antagonist at higher concentrations (Zava and Deuw, 1994). Genistein inhibits the tumour growth in various cancers in vitro and in vivo (Fotsis et al, 1995).…”