Repressive effect of the phytoestrogen genistein on estradiol-induced uterine leiomyoma cell proliferation

Miyake, A.; Takeda, Takashi; Isobe, Aki; Wakabayashi, Atsuko; Nishimoto, Fumihito; Morishige, Ken‐ichirou; Sakata, Masahiro; Kimura, Tadashi

doi:10.1080/09513590902730804

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…15,16 We selected a diet containing 600G and predicted that genistein would have advantageous effects on several markers of cardiovascular health. With this concentration of genistein in the diet, we routinely obtain plasma genistein levels of 7.7±4.0 µmol/L and 4.2±2.3 µmol/L in intact female and male mice, respectively, 12 indicating that continuous consumption of genistein can result in sustained plasma levels in the low µmol/L ranges.…”

Section: Discussionmentioning

confidence: 99%

A 2-month exposure to dietary genistein has sex-dependent effects on serum profile, cardiac protein expression, and aortic morphology in mice

Al‐Nakkash¹,

Martin²,

Cannon³

et al. 2014

NDS

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Background:The sex-dependent effects of chronic exposure to dietary genistein on cardiovascular health are poorly understood. Purpose: This study examined the effects of a genistein-containing diet on cardiovascular plasma markers, aortic morphology, blood pressure, and expression of cardioprotective proteins in male and female mice. Methods: C57BL/6J mice were fed either genistein diet (600 mg genistein/kg diet; 600G) or a genistein free diet (0G) for a period of 2 months. Results: After treatment, male and female mice fed 600G gained significantly less weight than their control counterparts fed 0G. Plasma insulin levels were significantly decreased in males only, whereas no changes in the other plasma markers were observed with 600G regardless of sex. Aortae from genistein-fed male mice demonstrated significant decreases in inner and outer luminal diameters and smooth muscle cell density. In female mice fed 600G, no changes in inner and outer luminal diameters were observed compared to female mice fed 0G, but smooth muscle cell density was significantly increased. Despite these differences in aortic morphology, no changes in arterial blood pressure were noted, regardless of sex or diet with genistein. Expression of cardiac glucose transporter type 4 (GLUT4) was increased in male hearts treated with genistein, while expression of endothelium nitric oxide synthase was significantly increased in females fed 600G compared to controls. However, no differences in inducible nitric oxide synthase protein were observed in all groups studied. Conclusion: Our data indicate that a 2-month diet with genistein results in changes in aortic morphology and expression of cardiac protein and its effects appear to be sex-dependent.

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Section: Discussionmentioning

confidence: 99%

A 2-month exposure to dietary genistein has sex-dependent effects on serum profile, cardiac protein expression, and aortic morphology in mice

Al‐Nakkash¹,

Martin²,

Cannon³

et al. 2014

NDS

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“…There is a concern that the isoflavones may mimic this action of estrogen [56]. However, a recent study on estrogen proliferation of ELT-3s cell also showed that genistein blocked this action of 17 β -estradiol [57]. Importantly, genistein's inhibitory effect was in turn attenuated by the PPAR γ inhibitor GW9662 [57].…”

Section: Association With Chronic Diseases: Cellular and Animal Momentioning

confidence: 99%

“…However, a recent study on estrogen proliferation of ELT-3s cell also showed that genistein blocked this action of 17 β -estradiol [57]. Importantly, genistein's inhibitory effect was in turn attenuated by the PPAR γ inhibitor GW9662 [57]. This underscores the likelihood that the action of isoflavones in mammals including man is multi-factorial and that PPAR signaling is a target of the isoflavones.…”

Section: Association With Chronic Diseases: Cellular and Animal Momentioning

confidence: 99%

“…For example, Dang elegantly showed that low concentrations (<1 μ M) of genistein stimulated osteogenesis whilst inhibiting adipogenesis in mesenchymal progenitor cells via ER mechanisms, whereas at slightly higher concentrations, the opposite response was observed which was mediated by PPAR γ activation [80]. Similarly, isoflavone-dependent activation of PPAR γ was shown to be important in the inhibition of estradiol-induced proliferation of uterine leiomyoma [57]. These latter examples highlight the potential for isoflavones to modulate estrogen signaling via indirect mechanisms and suggest a complex cross-talk between PPAR and ER signaling, that is regulated by isoflavones (Figure 5).…”

Section: Isoflavones and Cell Signaling: Activation Of Pparsmentioning

confidence: 99%

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Isoflavones and PPAR Signaling: A Critical Target in Cardiovascular, Metastatic, and Metabolic Disease

Patel

Barnes

2010

PPAR Research

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Isoflavone intake through foods and dietary supplements has both health advocates and critics. The latter come from a concern about the estrogenic effects of isoflavones in certain species. However, careful removal of isoflavones and other estrogens from the diet of rodents leads to the metabolic syndrome. These results suggest that isoflavones have other mechanisms of action, potentially those involving regulation of fatty acid metabolism via the nuclear receptors PPARα and PPARγ. The goal of this paper was to examine the evidence for isoflavone/PPAR signaling and to identify diseases in which such signaling would have an important impact. It is therefore of note that investigators using a chemical structure approach to discover PPAR ligands identified isoflavones as the best structures in the library of compounds that they tested. Future studies will involve careful identification of the underlying mechanisms whereby isoflavones have their action via PPAR signaling.

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“…In endometrial adenocarcinoma (Ishikawa) cells, both genistein and estrogen upregulated ER-stimulated gene activity and decreased estrogen-induced proliferation and stromal ER-β cell activation [185,186]. Genistein has suppressive effects on E2-stimulated ELT-3 cell proliferation in ELT-3 cells (uterine leiomyoma cell line) through PPARγ activation [187].…”

Section: Genital Cancersmentioning

confidence: 99%

Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits

Sharifi‐Rad

Quispe

Imran

et al. 2021

Oxidative Medicine and Cellular Longevity

169

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Genistein is an isoflavone first isolated from the brooming plant Dyer’s Genista tinctoria L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword “genistein” from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.

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Repressive effect of the phytoestrogen genistein on estradiol-induced uterine leiomyoma cell proliferation

Abstract: These experimental findings in vitro show that the repressive effect of genistein on E(2)-induced ELT-3 cell proliferation is through the activation of PPARgamma. Genistein may be useful as an alternative therapy for leiomyoma.

Cited by 12 publications

References 20 publications

A 2-month exposure to dietary genistein has sex-dependent effects on serum profile, cardiac protein expression, and aortic morphology in mice

A 2-month exposure to dietary genistein has sex-dependent effects on serum profile, cardiac protein expression, and aortic morphology in mice

Isoflavones and PPAR Signaling: A Critical Target in Cardiovascular, Metastatic, and Metabolic Disease

Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits

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