Inhibition of estrone sulfatase in human liver microsomes by quercetin and other flavonoids.
Inhibition of estrone sulfatase activity offers the potential for breast cancer prevention therapy by blocking a route to estrogen synthesis. We have investigated the inhibition of this activity by natural flavonoids in a human hepatic microsomal preparation in vitro. The majority of studies were performed with a male liver, but male and female livers exhibited comparable estrone sulfatase activities. The natural flavonoids, quercetin, kaempferol, and naringenin, significantly inhibited estrone sulfatase activity with I50 < 10 microM for the most potent, quercetin. Estrone sulfatase activity in the liver microsomes was biphasic, with a high affinity, low capacity, low concentration activity (Km 14.3 microM, Vmax 0.5 nmol/min/mg protein), probably steroid sulfatase-catalysed, and a low affinity, high capacity, high concentration activity (Km 1.5 mM, Vmax 21.5 nmol/min/mg protein), probably arylsulfatase C or E-catalysed. The former activity was inhibited uncompetitively by quercetin, the latter competitively. Quercetin, a natural dietary constituent, is a potent inhibitor of estrone sulfatase in vitro, and thus has the potential to express antiestrogenic activity in vivo.
Huang
Z
Z
Department of Environmental Health and Toxicology, University at Albany, State University of New York, USA.
Fasco
M J
MJ
Kaminsky
L S
LS
D000368:Aged; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D044949:Kaempferols; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013429:Sulfatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004965:Estrogen Antagonists; D044950:Flavanones; D005419:Flavonoids; D044949:Kaempferols; D012333:RNA, Messenger; C006552:kaempferol; D011794:Quercetin; D013429:Sulfatases; C020121:estrone sulfatase; C005273:naringenin