A. Purohit, G. Williams, C. J. Roberts
Sep 27, 1995
Citations
3
Influential Citations
79
Citations
Quality indicators
Journal
International Journal of Cancer
Abstract
Many tumours in endocrine‐sensitive tissues, such as the breast and endometrium, are hormone‐dependent and the hydrolysis of oestrone sulphate (EIS) to oestrone by oestrone sulphatase (EI‐STS) is a major source of oestrogen in such tumours. Oestrone‐3‐O‐sulphamate (EMATE) has been shown to be a potent EI‐STS inhibitor in vitro, and in this study its ability to inhibit enzyme activity in vivo was examined. EMATE was initially administered to female rats for 7 days, after which liver EI‐STS activity was measured. As EMATE also inhibits a related sulphatase in vitro, dehydroepiandrosterone sulphatase (DHA‐STS), its effect on the activity of this enzyme in vivo was also investigated. DHA‐STS has a pivotal role in regulating the synthesis of another steroid with potent oestrogenic properties, androstenediol. Administration of EMATE almost completely inhibited liver EI ‐STS (99%) and DHA‐STS (99%) activities and was active when given by the oral or subcutaneous routes. After a single dose of EMATE or following the cessation of multiple doses for 10 days, liver EI‐STS activity remained inhibited (>95%) for up to 7 and 10 days, respectively. Other compounds, such as 4‐hydroxytamoxifen and the “pure” anti‐oestrogen ICI 182,780, which are reported to inhibit EI‐STS activity in vitro, did not inhibit activity in vivo. In a preliminary study, EMATE, when injected over a 12‐day period, effectively reduced the growth of EI S‐stimulated nitrosomethyl‐urea‐induced mammary tumours in ovariectomised rats and inhibited tumour sulphatase activity in treated animals.