Inhibition of estrone sulfatase enzyme in human placenta and human breast carcinoma.
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| Abstract |
Estrone sulfatase is an important mechanism of local synthesis of biologically active estrogens in human breast cancer. The human placental microsome and breast carcinoma mitochondrial/microsomal estrone sulfatase activity were characterized and inhibition studies performed. The Km of the placental tissue enzyme was 6.83 microM, Vmax 0.015 nmol/min/mg, and for the breast carcinoma tissue Km was 8.91 microM and Vmax 0.022 nmol/min/mg. Danazol produced a significant inhibition of estrone sulfatase (20% with 50 microM danazol). No significant inhibition was seen in the presence of aminoglutethimide, rogletimide, tamoxifen, 4-hydroxyandrostenedione, stilboestrol, or any metabolites of danazol or tamoxifen. Studies with synthetic and naturally occurring steroids demonstrated that the presence of a sulfate group at the 3 position to be the most important factor in determining inhibition, and the most potent inhibitor was 5 alpha-androstene-3 beta,17 beta-diol-3-sulfate (Ki of 2.0 microM). The naturally occurring 3-sulfated steroids all demonstrated competitive inhibition. These studies could form the basis for the design of a potent estrone sulfatase inhibitor which would have potential therapeutic activity in the management of breast cancer.
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| Authors | T R Evans, M G Rowlands, M Jarman, R C Coombes |
| Journal | The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 39 Issue 4A Pg. 493-9 (Oct 1991) ISSN: 0960-0760 [Print] England |
| PMID | 1911438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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