Abstract
Dihydrogenistein (DHG) is one of the metabolites of genistein (GEN) found 'in the urine of human volunteers consuming soy. DHG differs from GEN by saturation of one double bond. In previous studies, we have shown that GEN produces a dose-dependent stimulatory effect on growth of MCF-7 cells [estrogen receptor (ER)-positive human breast cancer (HBC)] at concentrations from 1 nM to 1uM and a growth inhibitory effect at levels greater than 10 uM in both MCF-7 and MDA-231 (ER- negative HBC) cells. The effect of GEN on cell growth at lower concentration is mediated by an ER-mediated pathway and the effect of GEN at higher concentration is mediated by another mechanism, likely via protein tyrosine kinase inhibition. We evaluated the biological effects of DHG in HBC cells. We have demonstrated that DHG increased cell growth in a dose-dependent manner from 1 nM to 80uM in MCF-7 cells, but not in MDA-231 cells. However, DHG did not inhibit cell growth at higher concentration (above 25 uM) in either ER-positive or ER-negative HBC cells. Additionally, stimulation of pS2 mRNA expression by DHG occurred in a dose-dependent fashion from 1 nM to 80 uM in MCF-7 cells. In order to further confirm that DHG acts as an E agonist and elicits estrogenic effect by ER-mediated mechanism, we utilized the pure ER antagonist, ICI 164,384 (100nM), to block stimulation of pS2 expression and cell growth produced by DHG. These results suggest that minor modification of GEN results in loss of growth inhibitory effects at high (>25uM) concentrations of the isoflavone and no change in estrogenic activity.
Original language | English (US) |
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Pages (from-to) | A439 |
Journal | FASEB Journal |
Volume | 11 |
Issue number | 3 |
State | Published - 1997 |
Externally published | Yes |
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics