Article

Is soy consumption good or bad for the breast?

Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Journal of Nutrition (Impact Factor: 4.23). 10/2010; 140(12):2326S-2334S. DOI: 10.3945/jn.110.124230
Source: PubMed

ABSTRACT Genistein in soy activates estrogen receptor (ER)-α and ERβ and acts as an estradiol in multiple target tissues. Because estrogens increase breast cancer risk and genistein promotes the growth of ER-positive human breast cancer cells, it has remained unclear whether this isoflavone or soy is safe. Results reviewed here suggest that women consuming moderate amounts of soy throughout their life have lower breast cancer risk than women who do not consume soy; however, this protective effect may originate from soy intake early in life. We also review the literature regarding potential risks genistein poses for breast cancer survivors. Findings obtained in 2 recent human studies show that a moderate consumption of diet containing this isoflavone does not increase the risk of breast cancer recurrence in Western women, and Asian breast cancer survivors exhibit better prognosis if they continue consuming a soy diet. The mechanisms explaining the breast cancer risk-reducing effect of early soy intake or the protective effect in Asian breast cancer survivors remain to be established. We propose that the reduction in risk involves epigenetic changes that result in alterations in the expression of genes that regulate mammary epithelial cell fate, i.e. cell proliferation and differentiation. Lifetime soy consumption at a moderate level may prevent breast cancer recurrence through mechanisms that change the biology of tumors; e.g. women who consumed soy during childhood develop breast cancers that express significantly reduced Human epidermal growth factor receptor 2 levels. More research is needed to understand why soy intake during early life may both reduce breast cancer risk and risk of recurrence.

0 Followers
 · 
113 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies implicate dietary soy isoflavones as breast cancer preventives, especially due to their anti-estrogenic properties. However, soy isoflavones may also have a role in promoting breast cancer, which has yet to be clarified. We previously reported that equol, a metabolite of the soy isoflavone daidzein, may advance breast cancer potential via upregulation of the eukaryotic initiation factor 4GI (eIF4GI). In estrogen receptor negative (ER-) metastatic breast cancer cells, equol induced elevated levels of eIF4G which were associated with increased cell viability and the selective translation of mRNAs that use non-canonical means of initiation, including internal ribosome entry site (IRES), ribosome shunting, and eIF4G enhancers. These mRNAs typically code for oncogenic, survival, and cell stress molecules. Among those mRNAs translationally increased by equol was the oncogene and eIF4G enhancer, c-Myc. Here we report that siRNA-mediated knockdown of c-Myc abrogates the increase in cancer cell viability and mammosphere formation by equol, and results in a significant down-regulation of eIF4GI (the major eIF4G isoform), as well as reduces levels of some, but not all, proteins encoded by mRNAs that are translationally stimulated by equol treatment. Knockdown of eIF4GI also markedly reduces an equol-mediated increase in IRES-dependent mRNA translation and the expression of specific oncogenic proteins. However, eIF4GI knockdown did not reciprocally affect c-Myc levels or cell viability. This study therefore implicates c-Myc as a potential regulator of the cancer promoting effects of equol via upregulation of eIF4GI and selective initiation of translation on mRNAs that utilize non-canonical initiation, including certain oncogenes. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 01/2015; DOI:10.1074/jbc.M114.617415 · 4.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors (ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growth-promoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors (p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high (> 10) µmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability to inhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of "free" unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then exposes the future role that control of epigenetic modifications might play in prevention, prognostication, follow-up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi-drugs might have an increasing potential of development in the next future. However, if DNA Methyltransferase Inhibitors (DNMTi) and Histone Desacetylase Inhibitors (HDACi) have shown encouraging results in BC, their action remains non-specific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in co-treatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi-drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of Isothiocyanates (ITCs) from cruciferous vegetables or of Genistein (GE) from soybean in a dietary program that might potentially reduce the risk of BC in large populations. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 11/2014; DOI:10.1002/ijc.29347 · 5.01 Impact Factor

Preview

Download
0 Downloads
Available from