Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells.
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.
Brooks
Jennifer D
JD
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College St., Toronto, Ont., Canada M5S 3E2.
Thompson
Lilian U
LU
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008322:Mammals; D048789:Phytoestrogens / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D017705:Lignans; D048789:Phytoestrogens; D004958:Estradiol; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D019833:Genistein; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone