Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERα transcriptional activation in human breast cancer cells
The Journal of Steroid Biochemistry and Molecular Biology. 2008-05-01; 110(1-2): 176-185
DOI: 10.1016/j.jsbmb.2008.03.032
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1. J Steroid Biochem Mol Biol. 2008 May;110(1-2):176-85. doi:
10.1016/j.jsbmb.2008.03.032. Epub 2008 Apr 4.
Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have
different impact on ERalpha transcriptional activation in human breast cancer
cells.
Carreau C(1), Flouriot G, Bennetau-Pelissero C, Potier M.
Author information:
(1)Université de Bordeaux, Unité Micronutriments Reproduction Santé ENITA de
Bordeaux, 1 Cours du Général de Gaulle, CS 40201, 33175 Gradignan Cedex, France.
Lignans are plant compounds metabolized in the mammalian gut to produce the
estrogenic enterolignans, enterodiol (ED) and enterolactone (EL). Because
estrogens have been linked to breast cancer etiology, enterolignans could affect
breast cancer risk, but to our knowledge, the mechanisms by which they exert
their estrogenic and/or anti-estrogenic effects in humans are still unclear. To
better understand how estrogenic compounds from the food, such as the
enterolignans, might influence breast cancer progression and their mechanisms to
interfere with human estrogen receptor (ER) signalling in hormone-dependant
diseases, we examined and compared the ability of ED, EL and 17beta-estradiol
(E2) to induce the transactivation of ERalpha and ERbeta, to modulate ERalpha
target genes, to exert either growth stimulatory or anti-proliferative effects
and finally to modulate MCF-7 cell migration by acting on matrix
metalloproteases (MMP)-2 and -9, at concentrations that are achievable through a
lignan-rich diet. This study indicates that enterolignans show distinct
properties for transactivation of ERalpha and ERbeta. ED, as E2, induces ERalpha
transcriptional activation through transactivation functions AF-1 and AF-2,
while EL is less efficient in inducing AF-1, acting predominantly through AF-2.
Furthermore, ED and EL modulate ERalpha mRNA and protein contents as well as
MCF-7 cell proliferation and secreted MMP activities in a different way.
Enterolignans are compounds of wide interest nowadays and our results help to
unveil their mechanisms of action on ER, emphasizing the fact that the dietary
load in lignans could be of importance in the balance between being risk or
chemopreventive factors for breast cancer and women’s health.
DOI: 10.1016/j.jsbmb.2008.03.032
PMID: 18457947 [Indexed for MEDLINE]