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      Effects of Phytoestrogen Extracts Isolated from Elder Flower on Hormone Production and Receptor Expression of Trophoblast Tumor Cells JEG-3 and BeWo, as well as MCF7 Breast Cancer Cells

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          Abstract

          Herein we investigated the effect of elderflower extracts (EFE) and of enterolactone/enterodiol on hormone production and proliferation of trophoblast tumor cell lines JEG-3 and BeWo, as well as MCF7 breast cancer cells. The EFE was analyzed by mass spectrometry. Cells were incubated with various concentrations of EFE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the EFE on ERα/ERβ/PR expression was assessed by immunocytochemistry. EFE contains a substantial amount of lignans. Estradiol production was inhibited in all cells in a concentration-dependent manner. EFE upregulated ERα in JEG-3 cell lines. In MCF7 cells, a significant ERα downregulation and PR upregulation were observed. The control substances enterolactone and enterodiol in contrast inhibited the expression of both ER and of PR in MCF7 cells. In addition, the production of estradiol was upregulated in BeWo and MCF7 cells in a concentration dependent manner. The downregulating effect of EFE on ERα expression and the upregulation of the PR expression in MFC-7 cells are promising results. Therefore, additional unknown substances might be responsible for ERα downregulation and PR upregulation. These findings suggest potential use of EFE in breast cancer prevention and/or treatment and warrant further investigation.

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          Most cited references38

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          Selective estrogen-receptor modulators -- mechanisms of action and application to clinical practice.

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            Soy food intake and breast cancer survival.

            Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients. To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence. The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information. Total mortality and breast cancer recurrence or breast cancer-related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable. During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor-positive or -negative breast cancer and was present in both users and nonusers of tamoxifen. Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.
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              In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol.

              The metabolism of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol, and lariciresinol by human fecal microflora was investigated to study their properties as mammalian lignan precursors. The quantitative analyses of lignan precursors and the mammalian lignans enterolactone and enterodiol were performed by HPLC with coulometric electrode array detector. The metabolic products, including mammalian lignans, were characterized as trimethylsilyl derivatives by gas chromatography-mass spectrometry. Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol were converted to mammalian lignans only. Several metabolites were isolated and tentatively identified as for syringaresinol and arctigenin in addition to the mammalian lignans. Metabolites of 7-hydroxymatairesinol were characterized as enterolactone and 7-hydroxyenterolactone by comparison with authentic reference compounds. A metabolic scheme describing the conversion of the most abundant new mammalian lignan precursors, pinoresinol and lariciresinol, is presented.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                08 October 2016
                October 2016
                : 8
                : 10
                : 616
                Affiliations
                [1 ]Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University of Munich, Munich 80337, Germany; lennard.schroeder@ 123456med.uni-muenchen.de (L.S.); Christina.kuhn@ 123456med.uni-muenchen.de (C.K.); sandra.schulze@ 123456med.uni-muenchen.de (S.S.); tobias.weissenbacher@ 123456med.uni-muenchen.de (T.W.)
                [2 ]Department of Obstetrics and Gynaecology, University of Rostock, Rostock 18059, Germany; dagmar.richter@ 123456kliniksued-rostock.de
                [3 ]Department of Biological Sciences, University of Rostock, Rostock 18059, Germany; birgit.piechulla@ 123456uni-rostock.de (B.P.); chrobak@ 123456bni-hamburg.de (M.C.); sybille.abarzua@ 123456uni-rostock.de (S.A.)
                Author notes
                [* ]Correspondence: udo.jeschke@ 123456med.uni-muenchen.de ; Tel.: +49-89-51604240; Fax: +49-89-51604916
                Article
                nutrients-08-00616
                10.3390/nu8100616
                5084004
                27740591
                382dece1-37cf-4a22-a789-42e4aa44553b
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 July 2016
                : 22 September 2016
                Categories
                Article

                Nutrition & Dietetics
                lignans,isoflavones,elder flower,breast cancer,trophoblast tumor
                Nutrition & Dietetics
                lignans, isoflavones, elder flower, breast cancer, trophoblast tumor

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