the role of 17betahydroxysteroid dehydrogenases in modulating the activity of 2methoxyestradiol in breast cancer cells the bissulfamoylated derivative of 2methoxyestradiol 2meoe2 2methoxyestradiol317oobissulfamate 2meoe2bismate has shown potent antiproliferative and antiangiogenic activity in vitro and inhibits tumor growth in vivo 2meoe2bismate is bioavailable in contrast to 2meoe2 that has poor bioavailability in this study we have examined the role of 17betahydroxysteroid dehydrogenase 17betahsd type 2 in the metabolism of 2meoe2 in mdamb231 cells which express high levels of 17betahsd type 2 and in mcf7 cells transfected with 17betahsd type 2 highperformance liquid chromatography analysis showed that a significant proportion of 2meoe2 was metabolized to inactive 2methoxyestrone furthermore mcf7 cells transfected with 17betahsd type 2 were protected from the cytotoxic effects of 2meoe2 in contrast no significant metabolism of 2meoe2bismate was detected in transfected cells and 17betahsd type 2 transfection did not offer protection against 2meoe2bismate cytotoxicity this study may go some way to explaining the poor bioavailability of 2meoe2 as the gastrointestinal mucosa expresses high levels of 17betahsd type 2 in addition this study shows the value of synthesizing sulfamoylated derivatives of 2meoe2 with c17position modifications as these compounds have improved bioavailability and potency both in vitro and in vivo