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

Abstract

Listen

Translate article

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°C of physiological concentrations of estrone sulfate ([ 3H]-E 1S: 5×10 −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 (5×10 −8 to 5×10 −5 mol/l), in both cell lines. The IC 50 values were 1.93 μmol/l and 0.21 μmol/l in MCF-7 and T-47D cells, respectively. In another series of studies, after 24 h incubation at 37°C of physiological concentrations of estrone ([ 3H]-E 1: 5×10 −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: 5×10 −8 and 5×10 −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: 5×10 −6 and 5×10 −5 mol/l, medrogestone has no effect on MCF-7 cells, but inhibits the sulfotransferase activity in T-47D cells by −31.4% at 5×10 −5 mol/l. In conclusion, the inhibitory effect provoked by medrogestone on the enzyme involved in the biosynthesis of E 2 (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.