Effects of Phytoestrogen Extracts Isolated from Pumpkin Seeds on Estradiol Production and ER/PR Expression in Breast Cancer and Trophoblast Tumor Cells

Richter, Dagmar; Abarzua, Sibylle; Chrobak, Mareike; Vrekoussis, Thomas; Weißenbacher, Tobias; Kühn, Christina; Schulze, Sandra; Kupka, M.; Friese, Klaus; Briese, Volker; Piechulla, Birgit; Makrigiannakis, Antonis; Jeschke, Udo; Dian, Darius

doi:10.1080/01635581.2013.797000

Cited by 42 publications

(34 citation statements)

References 29 publications

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“…Despite the lack of independent effects of AI and FS on ERβ, each has been reported to affect expression of this receptor. Flaxseed lignans have been shown to down-regulate ERβ expression in estrogen-dependent MCF7 breast cancer cells (42), but conflicting effects have been reported for anastrozole (43, 44) Given the small sample size, the combination of AI and FS may have been necessary to produce the observed decreased ERβ expression.…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

McCann

Edge

Hicks

et al. 2014

Nutrition and Cancer

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Use of complementary approaches is common among breast cancer survivors. Potential interactions between aromatase inhibitors (AI) and high phytoestrogen foods, such as flaxseed (FS) are not often described. We conducted a pilot 2×2 factorial, randomized intervention study between tumor biopsy and resection, in 24 postmenopausal women with estrogen receptor positive (ER+) breast cancer, to assess the effects of flaxseed and anastrozole, and possible interactions between them, on serum steroid hormone and tumor-related characteristics associated with long-term survival (Roswell Park Cancer Institute, 2007–2010). The effect of each treatment vs placebo on outcomes was determined by linear regression adjusting for pre-treatment measure, stage, and grade. Although not statistically significant, mean ERβ expression was approximately 40% lower from pre- to post-intervention in the FS+AI group only. We observed a statistically significant negative association (β±SE −0.3±0.1; p=0.03) for androstenedione in the FS+AI group vs placebo and for DHEA with AI treatment (β±SE −1.6±0.6; p=0.009). Enterolactone excretion was much lower in the FS+AI group compared to the FS group. Our results do not support strong effects of flaxseed on AI activity for selected breast tumor characteristics or serum steroid hormone levels, but suggest AI therapy might reduce the production of circulating mammalian lignans from flaxseed.

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Section: Discussionmentioning

confidence: 99%

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

McCann

Edge

Hicks

et al. 2014

Nutrition and Cancer

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“…Genistein has been reported to alter the expression pattern of genes involved in invasion and metastasis in prostate cancer [31]. The ERα positive cell line MCF7 has been frequently used for the characterization of the effects of phytoestrogens on gene expression in breast cancer [32-36]. In most studies high concentrations of the compounds are used in order to obtain measurable effects.…”

Section: Phytoestrogensmentioning

confidence: 99%

Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

Albini¹,

Rosano²,

Ángelini³

et al. 2014

CMC

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Abstract:Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ER and ER and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto-and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).

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“…With the goal of identifying potential sources of phytoestrogens and selecting those with beneficial functions, our group has tested, in prior trials, the phytoestrogen properties of pumpkin and flax seed lignan and isoflavone extracts on the proliferation of trophoblast and breast cancer cell lines [18,19]. Moreover, the effect of the phytoestrogens genistein and daidzein on human term trophoblasts and their influence on fertility was investigated [20].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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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Effects of Phytoestrogen Extracts Isolated from Pumpkin Seeds on Estradiol Production and ER/PR Expression in Breast Cancer and Trophoblast Tumor Cells

Cited by 42 publications

References 29 publications

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

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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