Daidzein sulfoconjugates are potent inhibitors of sterol sulfatase (EC 3.1.6.2).
Recent studies have associated high dietary isoflavone intake with low incidence of breast cancer. Since estrogenic steroids are important factors in the evolution of breast cancer, and in breast tumors they are derived mainly from the sterol sulfatase pathway, we have therefore investigated effects of the isoflavone daidzein and its sulfoconjugates, daidzein-4'-O-sulfate and daidzein-7,4'-di-O-sulfate, on sterol sulfatase acitivity using dehydroepiandrosterone sulfate as substrate. While daidzein does not affect sterol sulfatase, its sulfoconjugates are potent inhibitors of this enzyme. Kinetic analyses reveal that daidzein-4'-O-sulfate and daidzein-7,4'-di-O-sulfate inhibit sterol sulfatase competitively with respect to the steroid substrate and with Ki values of 5.9 and 1 microM, respectively. Daidzein sulfo-conjugates also inhibit hydroxysteroid and phenol sulfotransferases but at much higher concentrations. These results provide a biochemical basis for the putative chemopreventive role of dietary isoflavones against breast cancer.
Wong
C K
CK
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Keung
W M
WM
D000818:Animals; D001192:Arylsulfatases / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000517:prevention & control; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008647:Mesocricetus; D043266:Steryl-Sulfatase; D015238:Sulfotransferases / Q000037:antagonists & inhibitors; D013463:Sulfuric Acid Esters / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D007529:Isoflavones; D013463:Sulfuric Acid Esters; C106370:daidzein-4'-O-sulfate; C106369:daidzein-7,4'-di-O-sulfate; C004742:daidzein; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase