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 (E2) 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 37 degrees C of physiological concentrations of estrone ([3H]-E1: 5 x 10(-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 6.65 +/- 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 (5 x 10(-8) and 5 x 10(-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 5 x 10(-7) mol/l in T-47D cells. At a high concentration (5 x 10(-5) mol/l) the stimulatory effect of nomegestrol acetate on the sulfotransferase activity was only 5.4% and 6.1%, 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.
Chetrite
Gérard Samuel
GS
Hormones and Cancer Research Unit, Institut de Puériculture, 26 Boulevard Brune, 75014 Paris, France.
Paris
Jacques
J
Shields-Botella
Jacqueline
J
Philippe
Jean-Claude
JC
Pasqualini
Jorge Raul
JR
D001711:Biotransformation; D001943:Breast Neoplasms / Q000201:enzymology*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008535:Megestrol / Q000494:pharmacology*; D009649:Norpregnadienes / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D015238:Sulfotransferases / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009649:Norpregnadienes; D045167:Progesterone Congeners; D004970:Estrone; C038501:nomegestrol acetate; D008535:Megestrol; D015238:Sulfotransferases; C020122:estrone sulfotransferase