Huang Z, Fasco M J, Kaminsky L S
Department of Environmental Health and Toxicology, University at Albany, State University of New York, USA.
J Steroid Biochem Mol Biol. 1997 Sep-Oct;63(1-3):9-15. doi: 10.1016/s0960-0760(97)00065-4.
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.
抑制雌酮硫酸酯酶活性通过阻断雌激素合成途径为乳腺癌预防治疗提供了可能性。我们在体外人肝微粒体制剂中研究了天然黄酮类化合物对该活性的抑制作用。大多数研究是用雄性肝脏进行的，但雄性和雌性肝脏表现出相当的雌酮硫酸酯酶活性。天然黄酮类化合物槲皮素、山奈酚和柚皮苷显著抑制雌酮硫酸酯酶活性，其中最有效的槲皮素的半数抑制浓度（I50）<10 microM。肝微粒体中的雌酮硫酸酯酶活性呈双相性，具有高亲和力、低容量、低浓度活性（Km 14.3 microM，Vmax 0.5 nmol/min/mg蛋白），可能由类固醇硫酸酯酶催化，以及低亲和力、高容量、高浓度活性（Km 1.5 mM，Vmax 21.5 nmol/min/mg蛋白），可能由芳基硫酸酯酶C或E催化。前一种活性被槲皮素非竞争性抑制，后一种活性被竞争性抑制。槲皮素是一种天然膳食成分，在体外是雌酮硫酸酯酶的有效抑制剂，因此有可能在体内发挥抗雌激素活性。
