Abstract
Phytoestrogens are a family of diverse polyphenolic compounds derived from nature plant that structurally or functionally mimic circulating estrogen in the mammalian reproductive system. They induce estrogenic and anti-estrogenic effects in the brain-pituitary-gonad axis (a principal endocrine system involving in reproductive regulation) and peripheral reproductive organs. The dichotomy of phytoestrogen-mediated actions elucidates that they play the biological activities via complex mechanisms and belong to various chemical classes. In comparison with their unobvious physiological functions in normal reproductive tissues, there are increasing investigations showing that phytoestrogen induces significant inhibitory effects on the growth of breast and ovarian cancers through different signaling pathways. This review summarized the results of the previous studies regarding principal signaling transductions for mediating the growth of the ovarian and breast cancers. Phytoestrogen potentially modulates the signaling molecules via: (1) blocking the nuclear and membrane estrogen receptors (ER), (2) interfering with the growth factor receptor, (3) inhibiting the G protein-coupled receptor in ER-deficient cells, (4) activating apoptosis and nullifying anti-apoptotic signals.
Highlights
Phytoestrogen refers a group of polyphenolic molecules originating from exogenous nature dietary plant source, including several family members such as flavones (Kaempferol and quercitin) (Fig. 1A), isoflavones (Fig. 1B), lignans, coumestanes (Fig. 1C), mycotoxins and stilbens (Fig. 1D) [1]
The dichotomy of classic estrogen receptors (ER) modulating action induced by phytoestrogen probably provides an explanation on conflicting evidence about the risks and benefits of dietary phytoestrogens in research presenting a contradictory picture in the mammalian reproductive system
It is speculated that phytoestrogen might not exhibit any significant toxicity or side-effect on the healthy reproductive organs, which needs to be clarified in the future
Summary
Phytoestrogen refers a group of polyphenolic molecules originating from exogenous nature dietary plant source, including several family members such as flavones (Kaempferol and quercitin) (Fig. 1A), isoflavones (genistein, daidzein, formononetin and equol) (Fig. 1B), lignans (enterolactone, enterodiol and nordihydroguaiaretic acid), coumestanes (coumestrol) (Fig. 1C), mycotoxins (zearalenol) and stilbens (resveratrol) (Fig. 1D) [1]. Phytoestrogen exhibits a low affinity for binding to ERα suggesting their weak estrogenic activities (10−2–10−3-fold) in comparison with E2, whereas they exert partial anti-estrogenic effect because of relatively preferentially binding to ERβ [1, 7]. In human aortic smooth muscle cells, phytoestrogen showed an inhibitory effect on mitogen-induced proliferation, migration and extracellular matrix synthesis via down-regulating the signaling pathway of mitogen-activated protein kinases (MAPK) [10]. We will focus on considering the multiple effects of these phytoestrogen molecules on circulating estrogen-regulated endocrine systems which are involved in controlling mammalian reproduction. We will summarize the biological activities of phytoestrogen on various signaling pathways in the mammalian breast and ovarian cancer cells
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