Control of sulfatase and sulfotransferase activities by medrogestone in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines

In the present study, we explored the effect of the progestin medrogestone on the sulfatase and sulfotransferase activities in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines, After 24 h incubation at 37 degrees C of physiological concentrations of estrone sulfate ([H-3]-E1S: 5 x 10(-9) mol/l), it was observed that this estrogen was converted in a great proportion to E-2 in both cell lines. Medrogestone significantly inhibits this transformation, at all the concentrations tested (5 x 10(-8) to 5 x 10(-5) mol/l), in both cell lines. The IC50 values were 1.93 mu mol/l and 0.21 mu mol/l in MCF-7 and T-47D cells, respectively. In another series of studies, after 24 h incubation at 37 degrees C of physiological concentrations of estrone ([H-3]-E-1: 5 x 10-9 mol/l), the sulfotransferase activity was detectable in both cell lines. Estrogen sulfates (ES) are found exclusively in the culture medium, which suggests that as soon as they are formed they are: excreted into the medium. Medrogestone has a biphasic effect on sulfotransferase activity in both cell lines. At low doses: 5 x 10(-8) and 5 x 10(-7) mol/l, this compound stimulates the enzyme by +73.5 and 52.7%, respectively, in MCF-7, and by 84.5 and 62.6% in T-47D cells. At high concentrations: 5 x 10(-6) and 5 x 10(-5) mol/l, medrogestone has no effect on MCF-7 cells, but inhibits the sulfotransferase activity in T-47D cells by -31.4% at 5 x 10(-5) mol/l. In conclusion, the inhibitory effect provoked by medrogestone on the enzyme involved in the biosynthesis of E2 (sulfatase pathway) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive ES, support a probable anti-proliferative effect of this progestin in breast tissue. Clinical applications of these findings can open new therapeutic possibilities for this disease. (C) 1999 Elsevier Science I,td. All rights reserved.