Effect of nomegestrol acetate on human estrogen sulfotransferase activity in the hormone-dependent MCF-7 and T-47D breast cancer cell lines

Breast cancer cells possess all the enzymes involved in the last steps of estradiol (E-2) bioformation, as well as in its transformation (e.g. sulfotransferases) for the conversion to estrogen sulfates (ES). As ES are biologically inactive, the formation of these conjugates is an important transformation pathway in the control of the hormone. In the present study, we explored the effect of nomegestrol acetate on the sulfotransferase activity in the hormone-dependent MCF-7 and T-47D human breast cancer cells. After 24-h incubation at 37degreesC of physiological concentrations of estrone ([H-3]-E-1: 5x10(-9) mol/l), it was observed that the sulfotransferase activity was present in both cell lines, since the concentrations of estrogen sulfates found were 9.40 +/- 1.10 in MCF-7 cells and 665 +/- 0.72 in the T-47D cells. The presence of ES was found exclusively in the culture medium, which suggests that as soon as the sulfate is biosynthesized it is secreted into the medium. Nomegestrol acetate has a stimulatory effect on sulfotransferase activity : at low doses (5x10(-8) and 5x10(-7) mol/l) this compound strongly increases the activity of this enzyme by 60.6% and 83%, respectively, in the MCF-7 cells and by 69.2% at 5x10(-7) mol/l in T-47D cells. At a high concentration (5x10(-5) mol/l) the stimulatory effect of nomegestrol acetate on the sulfotransferase activity was only 5.4% and 615, respectively, in MCF-7 and T-47D cells. In conclusion, the stimulation provoked at low doses by nomegestrol acetate on the estrogen sulfotransferase activity involved in the biosynthesis of the biologically inactive estrogen sulfates in hormone-dependent breast cancer cells is an important effect of this progestin and can open attractive clinical applications.