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Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks
Author(s) -
Rietjens Ivonne M. C. M.,
Sotoca Ana M.,
Vervoort Jacques,
Louisse Jochem
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200439
Subject(s) - isoflavones , genistein , phytoestrogens , daidzein , mode of action , estrogen receptor , epigenetics , cell growth , dna methylation , cancer cell , biology , cancer research , cancer , microbiology and biotechnology , estrogen , endocrinology , breast cancer , biochemistry , genetics , gene expression , gene
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 ER β, promoting apoptosis, with the major soy isoflavones genistein and daidzein activating especially ER β. 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.