Phytoestrogens and prevention of breast cancer: The contentious debate  

作　　者：Iqra Bilal Avidyuti Chowdhury Juliet Davidson Saffron Whitehead 

机构地区：[1]Department of Basic Medical Sciences, St George’s University of London

出　　处：《World Journal of Clinical Oncology》2014年第4期705-712,共8页世界临床肿瘤学杂志（英文版）

摘　　要：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 growthpromoting 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 toinhibit 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.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 growthpromoting 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 toinhibit 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.

关 键 词：PHYTOESTROGENS BREAST cancer CELL SIGNALLING CELL cycle EPIGENOMICS 

分 类 号：R737.9[医药卫生—肿瘤]