Selective inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1) reduces estrogen responsive cell growth of T47-D breast cancer cells

The most potent estrogen estradiol (E2) plays a pivotal role in the initiation and progression of estrogen dependent diseases. 17 beta-Hydroxysteroid dehydrogenase type 1 (17 beta HSD1) catalyses the NADPH-dependent E2-formation from estrone (E1). It is often overexpressed in breast cancer and endometriosis. For this reason, inhibition of 17 beta HSD1 is a promising strategy for the treatment of these diseases. In the present paper, we investigate the estrogen responsive cell growth of T47-D breast cancer cells, the intracellular inhibitory activity of non-steroidal 17 beta HSD1-inhibitors and their effects on estrogen dependent cell growth in vitro. At equal concentrations the estrogens E1 and E2 induced the same extent of growth stimulation indicating fast intracellular conversion of E1 into E2. Application of inhibitors selectively prevented stimulation of proliferation evoked by E1-treatment whereas E2-mediated stimulation was not affected. Furthermore, intracellular E2-formation from E1 was significantly inhibited with IC50-values in the nanomolar range. In conclusion, our findings strongly support suitability of non-steroidal 17 beta HSD1-inhibitors for the treatment of estrogen dependent diseases. (C) 2009 Elsevier Ltd. All rights reserved.