Phytoestrogens and breast cancer: In vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives

Basu, Paramita; Maier, Camelia

doi:10.1016/j.biopha.2018.08.100

Cited by 114 publications

(79 citation statements)

References 191 publications

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“…In contrast, phytoestrogens are non-steroidal compounds produced by plants. There are three known groups of phytoestrogens: isoflavones, coumestans, and lignans (Basu & Maier, 2018). Because phytoestrogens are chemically and structurally similar to estradiol, they can participate in both estrogenic and antiestrogenic effects through activation or blocking of the estrogen receptor ligand-binding domains (Turner, Agatonovic-Kustrin, & Glass, 2007).…”

Section: Endogenous and Exogenous Estrogen Receptors Ligandsmentioning

confidence: 99%

Estrogen receptor signaling mechanisms

Fuentes

Silveyra

2019

Advances in Protein Chemistry and Structural Biology

605

461

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The primary female sex hormones, estrogens, are responsible for the control of functions of the female reproductive system, as well as the development of secondary sexual characteristics that appear during puberty and sexual maturity. Estrogens exert their actions by binding to specific receptors, the estrogen receptors (ERs), which in turn activate transcriptional processes and/or signaling events that result in the control of gene expression. These actions can be mediated by direct binding of estrogen receptor complexes to specific sequences in gene promoters (genomic effects), or by mechanisms that do not involve direct binding to DNA (non-genomic effects). Whether acting via direct nuclear effects, indirect non-nuclear actions, or a combination of both, the effects of estrogens on gene expression are controlled by highly regulated complex mechanisms. In this chapter, we summarize the knowledge gained in the past 60 years since the discovery of the estrogen receptors on the mechanisms governing estrogen-mediated gene expression. We provide an overview of estrogen biosynthesis, and we describe the main mechanisms by which the female sex hormone controls gene transcription in different tissues and cell types. Specifically, we address the molecular events governing regulation of gene expression via the nuclear estrogen receptors (ERα, and ERβ) and the membrane estrogen receptor (GPER1). We also describe mechanisms of cross-talk between signaling cascades activated by both nuclear and membrane estrogen receptors. Finally, we discuss natural compounds that are able to target specific estrogen receptors and their implications for human health and medical therapeutics.

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Section: Endogenous and Exogenous Estrogen Receptors Ligandsmentioning

confidence: 99%

Estrogen receptor signaling mechanisms

Fuentes

Silveyra

2019

Advances in Protein Chemistry and Structural Biology

605

461

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“…Among food components, there are many phytochemicals showing estrogenic potency, which are known as phytoestrogens. These plant-derived polyphenols structurally and functionally mimic 17 β-estradiol by binding to the estrogen receptors-preferentially to the ERβ isoform, leading the prevention of ERα growth promotion activity [7]. Among polyphenolic compounds with phytoestrogen activity, there are isoflavones which can be found in food, especially in Asian countries.…”

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confidence: 99%

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Zakłos‐Szyda

Budryn

2020

Nutrients

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Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many cancers. Phytoestrogens’ structural resemblance to 17 β-estradiol allows their binding to ERβ isoform predominantly, and therefore, expression of genes connected with elevated proliferation, motility and invasiveness of cancer cells may be downregulated. Among polyphenolic compounds with phytoestrogenic activity, there are isoflavones from Trifolium pratense L. (red clover) sprouts, containing high amounts of formononetin and biochanin A and their glycosides. To determine the source of the most biologically active isoflavones, we obtained four extracts from sprouts before and after their lactic fermentation and/or β-glucosidase treatment. Our previous results of ITC (isothermal titration calorimetry) modelling and a docking simulation showed clover isoflavones’ affinity to ERβ binding, which may downregulate cancer cell proliferation and migration. Thus, the biological activity of T. pratense sprouts’ extracts was checked under in vitro conditions against highly invasive human breast cancer cell line MDA-MB-231 and non-invasive human breast cancer cell line MCF-7 cells. To compare extracts’ activities acquired for cancer cells with those activities against normal cells, as a third model we choose human umbilical vein endothelial cells (HUVEC), which, due to their migration abilities, are involved in blood vessel formation. Extracts obtained from fermented sprouts at IC0 dosages were able to inhibit migration of breast cancer cells through their influence on intracellular ROS generation; membrane stiffening; adhesion; regulation of MMP-9, N-cadherin and E-cadherin at transcriptional level; or VEGF secretion. Simultaneously, isolated phenolics revealed no toxicity against normal HUVEC cells. In the manuscript, we proposed a preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones. In this manner, T. pratense sprouts, especially after their lactic fermentation, can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties.

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“…In addition, several studies reported that some of the estrogen receptor (ER)-mediated responses induced by flavonoids are comparable, or even superior, to those induced by physiological levels of estradiol [47]. Thus, some flavonoids are still described as complete estrogen agonists and with a higher affinity for ERβ, exerting a response that opposes the proliferative effects of ERα activation [48,49]. This suggests that, at physiological levels, phytoestrogens can activate ERβ but not procancer signaling mediated by ERα (or activate it to a much lesser extent) enabling a beneficial antiproliferative effect.…”

Section: Discussionmentioning

confidence: 99%

Association between Polyphenol Intake and Breast Cancer Risk by Menopausal and Hormone Receptor Status

et al. 2020

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There is limited evidence of phenolic compounds acting as protective agents on several cancer types, including breast cancer (BC). Nevertheless, some polyphenol classes have not been investigated and there is a lack of studies assessing the effect on menopausal status and hormone receptor status as influenced by these compounds. The objective of this study is to evaluate the association between the intake of all polyphenol classes in relation to the BC risk by menopausal and hormone receptor status. We used data from a population-based multi-case-control study (MCC-Spain) including 1472 BC cases and 1577 controls from 12 different regions of Spain. The odds ratios (ORs) with 95% CI were calculated using logistic regression of mixed effects by quartiles and log2 of polyphenol intakes (adjusted for the residual method) of overall BC, menopausal and receptor status. No associations were found between total intake of polyphenols and BC risk. However, inverse associations were found between stilbenes and all BC risk (ORQ4 vs. Q1: 0.70, 95%CI: 0.56–0.89, Ptrend = 0.001), the consumption of hydroxybenzaldehydes (ORQ4 vs. Q1: 0.75, 95%CI: 0.59–0.93, Ptrend = 0.012) and hydroxycoumarins (ORQ4 vs. Q1: 0.73, 95%CI: 0.57–0.93; Ptrend = 0.005) were also inversely associated. The intake of stilbenes, hydroxybenzaldehydes and hydroxycoumarins can contribute to BC reduction risk on all menopausal and receptor statuses.

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Phytoestrogens and breast cancer: In vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives

Cited by 114 publications

References 191 publications

Estrogen receptor signaling mechanisms

Estrogen receptor signaling mechanisms

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Association between Polyphenol Intake and Breast Cancer Risk by Menopausal and Hormone Receptor Status

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