Estrogen effects of Daldinia concentrica and Psathyrella efflorescens extracts in vitro.
ABSTRACT Daldinia concentrica and Psathyrella efflorescens are two fungi used in African traditional medicine. In the present study, their extracts were evaluated for their steroid activities in estrogen- or androgen-dependent cell lines using as endpoints steroid-dependent transcriptional activity and cell proliferation. Treatment of human breast cancer MCF-7 cells with 15 or 30 microg/ml of Daldinia concentrica or Psathyrellaefflorescens extracts in the absence of 17beta-estradiol (E2) significantly increased the transcriptional activity of an estrogen receptor (ER)-dependent reporter gene, in the same range as E2. Similar data were obtained in gonadotrope cell line alpha-T3-1. All the effects were prevented by the pure estrogen antagonist, ICI 182,780. In the absence of steroid addition, the two extracts induced cell proliferation of ER-dependent MCF-7 and Ishikawa Var-I cell lines by approximately 100% of the E2 response. Combination treatments with E2 showed no competitive or additive effects in the two latter cell lines. Interestingly, the extracts had no androgen-like response in androgen receptor (AR)-positive and ER-negative MDA-MB231 cells, suggesting that fungi effects are estrogen specific and extracts are not toxic at used concentrations. Results provided evidence that Daldinia concentrica or Psathyrellaefflorescens extracts induce estrogen-like effects in ER-positive cell lines, which could be responsible of the effects observed in vivo.
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ABSTRACT: Ligands for the nuclear receptor superfamily control many aspects of biology, including development, reproduction, and homeostasis, through regulation of the transcriptional activity of their cognate receptors. Selective receptor modulators (SRMs) are receptor ligands that exhibit agonistic or antagonistic biocharacter in a cell- and tissue context-dependent manner. The prototypical SRM is tamoxifen, which as a selective estrogen receptor modulator, can activate or inhibit estrogen receptor action. SRM-induced alterations in the conformation of the ligand-binding domains of nuclear receptors influence their abilities to interact with other proteins, such as coactivators and corepressors. It has been postulated, therefore, that the relative balance of coactivator and corepressor expression within a given target cell determines the relative agonist vs. antagonist activity of SRMs. However, recent evidence reveals that the cellular environment also plays a critical role in determining SRM biocharacter. Cellular signaling influences the activity and subcellular localization of coactivators and corepressors as well as nuclear receptors, and this contributes to gene-, cell-, and tissue-specific responses to SRM ligands. Increased understanding of the effect of cellular environment on nuclear receptors and their coregulators has the potential to open the field of SRM discovery and research to many members of the nuclear receptor superfamily.Endocrine Reviews 03/2004; 25(1):45-71. · 14.87 Impact Factor
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ABSTRACT: There is currently much concern that a wide range of both synthetic and naturally occurring environmental chemicals may act as endocrine disruptors (ED), and may adversely affect humans and wildlife. We examined the estrogenic effects of the phytoestrogens daidzein (DAI), equol (EQU) and O-desmethylangolensin (O-DMA), two metabolites of DAI, in three different assays. Binding affinity to the estrogen receptor alpha was 1000-10,000-fold lower compared with the endogenous estrogen estradiol. In the receptor positive cell line MCF-7 the phytoestrogens induced the expression of a reporter gene. The E-SCREEN is based on the estrogen-receptor binding induced proliferation of the human breast cancer cell line MCF-7. We also adapted the E-SCREEN for the estrogen-receptor positive human ovarian cancer cell line BG-1. The tested phytoestrogens induced cell proliferation in both cell lines, but not in the receptor negative human breast cancer cell line MDA-MB-231. The phytoestrogen-induced cell proliferation could be blocked by addition of the receptor antagonist 4-hydroxytamoxifen (OHT). Combination treatments with the endogenous estrogen estradiol showed competitive effects in MCF-7 cells. These studies demonstrated that the tested phytoestrogens exerted estrogenic responses in cells derived from two different tissues, breast and ovary. Furthermore, we demonstrated that BG-1 cells are a suitable additional cell system to investigate estrogenicity of test compounds.Toxicology in Vitro 01/2001; 15(4-5):433-9. · 2.65 Impact Factor
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ABSTRACT: There is an intense discussion in the scientific and even more so in the public community as well as regulatory agencies about the potential benefits or detrimental effects of plant-derived compounds that may affect the endocrine system, especially estrogen signaling pathways. These so-called phytoestrogens are found in the normal western diet and predominantly in an eastern or soy-based diet and the potency of the isolated compounds to interact with the known receptors for estrogen varies tremendously. The estrogen receptors, ER alpha and ER beta, mediate the effects of endogenous estrogens, i.e. regulation of reproductive function, tissue development, cell proliferation and differentiation. In this review, in vitro test systems available to date for the screening of estrogenic and antiestrogenic activity including mechanism-based assays are described. The potency of phytoestrogens determined using these in vitro assays are compared with the potency of endogenous estrogens and results obtained in vitro are compared with effects in vivo. Finally, the impact of in vitro assays to determine estrogenicity on human hazard assessment is discussed as well as other non ER-mediated mechanisms that may contribute to potential beneficial or adverse effects of phytoestrogens in man.Journal of Chromatography B 10/2002; 777(1-2):155-65. · 2.49 Impact Factor