Soy Isoflavones Have an Antiestrogenic Effect and Alter Mammary Promoter Hypermethylation in Healthy Premenopausal Women

Qin, Wenyi; Zhu, Weizhu; Shi, Huidong; Hewett, John E.; Ruhlen, Rachel L.; MacDonald, Ruth S.; Rottinghaus, George E.; Chen, Yin Chieh; Sauter, Edward R.

doi:10.1080/01635580802404196

Cited by 126 publications

(87 citation statements)

References 36 publications

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“…In one study, genistein (300 mg/kg diet) altered the methylation profile of wild-type mouse prostate tissue [61] . In healthy premenopausal women, consumption of higher levels of genistein (90.6 mg/day) and daidzein (36.4 mg/day) for one menstrual cycle was associated with increased methylation of RAR ␤ and the cell cycle regulator cyclin D2 ( CCND2 ) in breast samples, although the significance of these results is not clear [62] .…”

Section: Polyphenolsmentioning

confidence: 73%

Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

2011

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Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone posttranslational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated.

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Section: Polyphenolsmentioning

confidence: 73%

Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

2011

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“…A randomized, double-blind trial conducted on premenopausal healthy women (n=34) to determine the effect isoflavones, including genistein, daidzein, and glycitein taken daily (40 or 140 mg) through one menstrual cycle, on the methylation status of p16, RASSF1A, RARb2, ER, and CCND2 genes known to be silenced due to hypemethylation of their promoters in breast cancer. The RARb2 and CCND2 methylation was found increased in intraductal specimens after treatment which correlated with genistein concentration in the serum (71).…”

Section: Genistein and Soy Isoflavonesmentioning

confidence: 82%

Plant Phytochemicals as Epigenetic Modulators: Role in Cancer Chemoprevention

Thakur

Deb

Babcook

et al. 2013

AAPS J

142

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Abstract. In recent years, "nutri-epigenetics," which focuses on the influence of dietary agents on epigenetic mechanism(s), has emerged as an exciting novel area in epigenetics research. Targeting of aberrant epigenetic modifications has gained considerable attention in cancer chemoprevention research because, unlike genetic changes, epigenetic alterations are reversible and occur during early carcinogenesis. Aberrant epigenetic mechanisms, such as promoter DNA methylation, histone modifications, and miRNA-mediated post-transcriptional alterations, can silence critical tumor suppressor genes, such as transcription factors, cell cycle regulators, nuclear receptors, signal transducers, and apoptosis-inducing and DNA repair gene products, and ultimately contribute to carcinogenesis. In an effort to identify and develop anticancer agents which cause minimal harm to normal cells while effectively killing cancer cells, a number of naturally occurring phytochemicals in food and medicinal plants have been investigated. This review highlights the potential role of plant-derived phytochemicals in targeting epigenetic alterations that occur during carcinogenesis, by modulating the activity or expression of DNA methyltransferases, histone modifying enzymes, and miRNAs. We present in detail the epigenetic mode of action of various phytochemicals and discuss their potential as safe and clinically useful chemopreventive strategies.

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“…Qin et al, 2014) or effects of isoflavones on DNA methylation (W. Y. Qin et al, 2009) or microRNAs (Xia et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation

Velpen

Veer

Islam

et al. 2016

Food and Chemical Toxicology

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Quantitative insight into species differences in risk assessment is expected to reduce uncertainty and variability related to extrapolation from animals to humans. This paper explores quantification and comparison of gene expression data between tissues and species from intervention studies with isoflavones.Gene expression data from peripheral blood mononuclear cells (PBMCs) and white adipose tissue (WAT) after 8wk isoflavone interventions in postmenopausal women and ovariectomized F344 rats were used. A multivariate model was applied to quantify gene expression effects, which showed 3 to 5-fold larger effect sizes in rats compared to humans.For estrogen responsive genes, a 5-fold greater effect size was found in rats than in humans.For these genes, intertissue correlations (r=0.23 in humans, r=0.22 in rats) and interspecies correlation in WAT (r=0.31) were statistically significant. Effect sizes, intertissue and interspecies correlations for some groups of genes within energy metabolism, inflammation and cell cycle processes were significant, but weak.Quantification of gene expression data reveals differences between rats and women in effect magnitude after isoflavone supplementation. For risk assessment, quantification of gene expression data and subsequent calculation of intertissue and interspecies correlations within biological pathways will further strengthen knowledge on comparability between tissues and species.

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Soy Isoflavones Have an Antiestrogenic Effect and Alter Mammary Promoter Hypermethylation in Healthy Premenopausal Women

Cited by 126 publications

References 36 publications

Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

Plant Phytochemicals as Epigenetic Modulators: Role in Cancer Chemoprevention

A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation

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