title: Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks.
abstract: Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic mode of action. One mechanism relates to the different ultimate cellular effects of activation of estrogen receptor (ER) α, promoting cell proliferation, and of ERβ, promoting apoptosis, with the major soy isoflavones genistein and daidzein activating especially ERβ. A second mode of action includes the role of epigenetics, including effects of isoflavones on DNA methylation, histone modification and miRNA expression patterns. The overview presented reveals that we are only at the start of unraveling the complex underlying mode of action for effects of isoflavones, both beneficial or adverse, on cell proliferation and cancer risks. It is evident that whatever model system will be applied, its relevance to human tissues with respect to ERα and ERβ levels, co-repressor and co-activator characteristics as well as its relevance to human exposure regimens, needs to be considered and defined.
authors.affiliation: Division of Toxicology, Wageningen University, 6703 HE Wageningen, The Netherlands. ivonne.rietjens@wur.nl
authors.forename: Ivonne M C M
authors.initials: IM
authors.lastname: Rietjens
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sotoca
authors.forename: Jacques
authors.initials: J
authors.lastname: Vervoort
authors.forename: Jochem
authors.initials: J
authors.lastname: Louisse
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control*; D048789:Phytoestrogens / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D012307:Risk Factors; D013025:Glycine max / Q000737:chemistry*
chemical_list: D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006657:Histones; D007529:Isoflavones; D035683:MicroRNAs; D048789:Phytoestrogens; D010936:Plant Extracts; C004742:daidzein; D019833:Genistein