Lack of an Inducible Effect of Dietary Soy Isoflavones on the mRNA Abundance of Hepatic Cytochrome P-450 Isozymes in Rats

Kishida, Taro; Nagamoto, Manabu; Ohtsu, Yohhei; Watakabe, Miho; Ohshima, Daisuke; Nashiki, Kunitaka; Maekawa, Takafumi; Izumi, Tohru; Obata, Akio; Ebihara, Kiyoshi

doi:10.1271/bbb.68.508

Cited by 23 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data on dietary soy isoflavone exposure in monkeys are consistent with findings from Kishida and colleagues who reported no effect of dietary soy isoflavones on hepatic CYP mRNA expression in rats (35). These results do not however rule out a direct effect of isoflavones on CYP enzyme activity as opposed to an estrogen receptor or aryl-hydrocarbon receptor-mediated transcriptional mechanism, which explains most variation observed in CYP activity (36).…”

Section: Discussionsupporting

confidence: 92%

Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes

Scott

Durant

Leone-Kabler

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Estrogen exposure and metabolism may play an important role in the development of estrogensensitive cancers in postmenopausal women. In this study we investigated whether past oral contraceptive (OC) administration or current dietary isoflavonoids (IF) affected expression and/or activity of steroid hormone-metabolizing cytochrome P450 (CYP) enzymes using complementary primate and cell culture models. One-hundred-eighty-one female cynomolgus macaques were randomized to receive OC or nothing for 26 months premenopausally, then ovariectomized and randomized to one of three diets for 36 months: an IF-depleted soy protein isolate (Soy−) diet, a Soy diet with IF (Soy+), or a Soy− diet supplemented with conjugated equine estrogens (CEE). Prior OCtreatment significantly reduced CYP gene expression in the mammary gland (≤60% of OC−). Dietary IFs had no effect on CYP expression, while CEE-treatment decreased CYP1A1 and increased CYP3A4 mRNA in a tissue-specific manner. For in vitro studies, we measured effects of the isoflavonoids genistein, daidzein and equol on CYP activity using intact V79 cells stably transfected to express CYP1A1, CYP1B1, or CYP3A4. All three IFs significantly altered CYP activity in a dosedependent and isoform-specific manner (20-95% inhibition vs. controls). These results suggest potential mechanisms for prior OC and dietary IF effects on cancer risk in estrogen-responsive tissues.

show abstract

Section: Discussionsupporting

confidence: 92%

Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes

Scott

Durant

Leone-Kabler

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

show abstract

“…It is unclear how to explain these conflicting findings. Since GEN does not alter the expression of TAM metabolizing enzymes [40], nor is there any evidence that increased estrogenicity impairs antiestrogen action, as TAM elevates circulating estrogen levels [41], the opposing effects of GEN on human breast cancer cells in vitro or in vivo and on breast cancer patients are unlikely to reflect estrogenicity of this isoflavone.…”

Section: Discussionmentioning

confidence: 99%

Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats

Zhang

Cook

Wärri

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose Whether it is safe for estrogen receptor positive (ER+) breast cancer patients to consume soy isoflavone genistein (GEN) remains controversial. We compared the effects of GEN intake mimicking either Asian (lifetime) or Caucasian (adulthood) intake patterns to that of starting its intake during tamoxifen (TAM) therapy using a preclinical model. Experimental Design Female Sprague-Dawley rats were fed an AIN93G diet supplemented with 0 (control diet) or 500 ppm GEN from postnatal day 15 onwards (lifetime GEN). Mammary tumors were induced with 7,12-dimethylbenz(a)anthracene (DMBA), after which a group of control diet fed rats were switched to GEN diet (adult GEN). When the first tumor in a rat reached 1.4 cm in diameter, TAM was added to the diet, and a subset of previously only control diet fed rats also started GEN intake (post-diagnosis GEN). Results Lifetime GEN intake reduced de novo resistance to TAM, compared with post-diagnosis GEN groups. Risk of recurrence was lower both in the lifetime and adult GEN groups than in the post-diagnosis GEN group. We observed downregulation of unfolded protein response (UPR) and autophagy related genes (GRP78, IRE1α, ATF4 and Beclin-1), and genes linked to immunosuppression (TGFβ and Foxp3), and upregulation of cytotoxic T cell marker CD8a in the tumors of the lifetime GEN group, compared with controls, post-diagnosis, and/or adult GEN groups. Conclusions GEN intake mimicking Asian consumption patterns improved response of mammary tumors to TAM therapy, and this effect was linked to reduced activity of UPR and pro-survival autophagy signaling, and increased anti-tumor immunity.

show abstract

“…As noted in earlier sections, isoflavones have been described as agonists as well as antagonists of the AhR. Thus, it is not surprising that studies report a direct induction of CYP1A1 expression mediated by isoflavones [226,227,228,237], while other studies did not report such results [242,243]. …”

Section: Introductionmentioning

confidence: 93%

Potential Health-modulating Effects of Isoflavones and Metabolites via Activation of PPAR and AhR

2010

View full text Add to dashboard Cite

Isoflavones have multiple actions on cell functions. The most prominent one is the activation of estrogen receptors. Other functions are often overlooked, but are equally important and explain the beneficial health effects of isoflavones. Isoflavones are potent dual PPARα/γ agonists and exert anti-inflammatory activity, which may contribute to the prevention of metabolic syndrome, atherosclerosis and various other inflammatory diseases. Some isoflavones are potent aryl hydrocarbon receptor (AhR) agonists and induce cell cycle arrest, chemoprevention and modulate xenobiotic metabolism. This review discusses effects mediated by the activation of AhR and PPARs and casts a light on the concerted action of isoflavones.

show abstract

Lack of an Inducible Effect of Dietary Soy Isoflavones on the mRNA Abundance of Hepatic Cytochrome P-450 Isozymes in Rats

Cited by 23 publications

References 24 publications

Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes

Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes

Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats

Potential Health-modulating Effects of Isoflavones and Metabolites via Activation of PPAR and AhR

Contact Info

Product

Resources

About