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Glyceollin I enantiomers distinctly regulate ER-mediated gene expression.
- Source :
-
Steroids [Steroids] 2010 Dec; Vol. 75 (12), pp. 870-8. Date of Electronic Publication: 2010 May 21. - Publication Year :
- 2010
-
Abstract
- Glyceollins are pterocarpan phytoalexins elicited in high concentrations when soybeans are stressed. We have previously reported that the three glyceollin isomers (GLY I-III) exhibit antiestrogenic properties, which may have significant biological effects upon human exposure. Of the three isomers, we have recently shown that glyceollin I is the most potent antiestrogen. Natural (-)-glyceollin I recently was synthesized along with its racemate and unnatural (+) enantiomer. In this study, we compared the glyceollin I enantiomers' ER binding affinity, ability to inhibit estrogen responsive element transcriptional (ERE) activity and endogenous gene expression in MCF-7 cells. The results demonstrated similar binding affinities for both ERalpha and ERbeta. Reporter gene assays in MCF-7 cells revealed that while (+)-glyceollin I slightly stimulated ERE transcriptional activity, (-)-glyceollin I decreased activity induced by estrogen. Co-transfection reporter assays performed in HEK 293 cells demonstrated that (+)-glyceollin I increased ERE transcriptional activity of ERalpha and ERbeta with and without estrogen with no antiestrogenic activity observed. Conversely, (-)-glyceollin I decreased the activity of both ER subtypes stimulated by estradiol demonstrating potent antiestrogenic properties. Additionally, each Gly I enantiomer induced unique gene expression profiles in a PCR array panel of genes commonly altered in breast cancer.<br /> (Copyright 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Estrogen Receptor alpha chemistry
Estrogen Receptor beta chemistry
HEK293 Cells
Humans
Models, Molecular
Protein Conformation
Pterocarpans metabolism
Response Elements genetics
Stereoisomerism
Substrate Specificity
Transcriptional Activation drug effects
Estrogen Receptor alpha metabolism
Estrogen Receptor beta metabolism
Gene Expression Regulation drug effects
Pterocarpans chemistry
Pterocarpans pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5867
- Volume :
- 75
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Steroids
- Publication Type :
- Academic Journal
- Accession number :
- 20493896
- Full Text :
- https://doi.org/10.1016/j.steroids.2010.05.007