Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERalpha transcriptional activation in human breast cancer cells.
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.
Carreau
Charlotte
C
Université de Bordeaux, Unité Micronutriments Reproduction Santé ENITA de Bordeaux, 1 Cours du Général de Gaulle, CS 40201, 33175 Gradignan Cedex, France.
Flouriot
Gilles
G
Bennetau-Pelissero
Catherine
C
Potier
Mylène
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017705:Lignans / Q000378:metabolism / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology; D059808:Polyphenols; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects*
D047628:Estrogen Receptor alpha; D005419:Flavonoids; D017705:Lignans; D010636:Phenols; D048789:Phytoestrogens; D059808:Polyphenols; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone