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Updated: Aug 18, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7
Jennifer D Brooks1, Lilian U Thompson
1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College St., Toronto, Ont., Canada M5S 3E2.
Abstract:
Estrogen plays a major role in breast cancer development and progression. Breast tissue and cell lines contain the necessary enzymes for estrogen synthesis, including aromatase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). These enzymes can influence tissue exposure to estrogen and therefore have become targets for breast cancer treatment and prevention. This study determined whether the isoflavone genistein (GEN) and the mammalian lignans enterolactone (EL) and enterodiol (ED) would inhibit the activity of aromatase and 17beta-HSD type 1 in MCF-7 cancer cells, thereby decreasing the amount of estradiol (E2) produced and consequently cell proliferation. Results showed that 10 microM EL, ED and GEN significantly decreased the amount of estrone (E1) produced via the aromatase pathway by 37%, 81% and 70%, respectively. Regarding 17beta-HSD type 1, 50 microM EL and GEN maximally inhibited E2 production by 84% and 59%, respectively. The reduction in E1 and E2 production by EL and the reduction in E2 production by GEN were significantly related to a reduction in MCF-7 cell proliferation. 4-Hydroxyandrostene-3,17-dione (50 microM) did not inhibit aromatase but inhibited the conversion of E1 to E2 by 78%, suggesting that it is a 17beta-HSD type 1 inhibitor. In conclusion, modulation of local E2 synthesis is one potential mechanism through which ED, EL and GEN may protect against breast cancer.
Insights
Dietary compounds enterolactone (EL), enterodiol (ED), and genistein (GEN) inhibit key enzymes in estrogen synthesis, reducing breast cancer cell proliferation. These findings suggest a potential mechanism for breast cancer prevention by modulating local estrogen production.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Estrogen is a key driver in breast cancer development and progression.
- Enzymes like aromatase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) are crucial for estrogen synthesis in breast tissue.
- Targeting these enzymes offers a strategy for breast cancer treatment and prevention.
Purpose of the Study:
- To investigate the inhibitory effects of genistein (GEN), enterolactone (EL), and enterodiol (ED) on aromatase and 17beta-HSD type 1 activity in MCF-7 breast cancer cells.
- To determine if these compounds reduce estradiol (E2) production and subsequent cancer cell proliferation.
Main Methods:
- MCF-7 cells were treated with varying concentrations of EL, ED, and GEN.
- Estrone (E1) and estradiol (E2) production were measured to assess enzyme inhibition.
- Cell proliferation was quantified to correlate with reduced estrogen synthesis.
Main Results:
- EL, ED, and GEN significantly inhibited estrone (E1) production via aromatase.
- EL and GEN markedly reduced estradiol (E2) production by inhibiting 17beta-HSD type 1.
- Inhibition of E1 and E2 production by EL and GEN correlated with reduced MCF-7 cell proliferation.
Conclusions:
- Enterodiol (ED), enterolactone (EL), and genistein (GEN) modulate local estrogen synthesis by inhibiting key enzymes.
- This modulation of estrogen production represents a potential mechanism for breast cancer chemoprevention.
