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.

Clinical and Biologic Activity of an Estrogenic Herbal Combination (PC-SPES) in Prostate Cancer

“…10 Although PC-SPES is promoted as a nonestrogenic food supplement, some of its constituents have estrogenic activity. [6][7][8] Licorice competes with estradiol in an estrogen-receptor-binding assay, 11 and ginseng induces estrogen-regulated expression of pS2, a small protein found in breast cancer, in cultured MCF-7 breastcancer cells. 12 The clinical implications of such activities are unknown.…”

Rethinking Breast Cancer Risk and the Environment: The Case for the Precautionary Principle

“…Many are "good" xenoestrogens that bind strongly with the ER and appear to have protective effects. Several of these are found in plants, e.g., daidzein, genistein, isoflavonoids, as well as in fish oil (41)(42)(43). Some of them appear to serve as antioxidants.…”

Avoidable Causes of Breast Cancer: The Known, Unknown, and the Suspected

“…In fact, ovariectomy in women under age 30 effectively prevents breast cancer. Reducing estrogen levels overall slows breast cell proliferation, induces cell death or apoptosis, and inhibits aromatase 9 …”

“…Recent studies indicate that common concentrations of some synthetic xenoestrogens may be many times more potent when encountered as mixtures than as individual compounds 8 . Some xenohormones, such as those in plants, appear to be excreted rapidly and occur with other factors such as fiber and micronutrients that appear to be generally protective against breast cancer 9 . In contrast, some synthetic xenohormones can persist for decades in the body and generate free radicals that damage DNA or otherwise promote aberrant cell growth 10 .…”