Control of Sulfatase Activity by Nomegestrol Acetate in Normal and Cancerous Human Breast Tissues

Nomegestrol acetate (NOMAC), a 17·-hydroxy- nor-progesterone derivative (17·-acetoxy-6-methyl-19-nor-4,6- pregnadiene-3,20-dione, the active substance in Lutenyl ® ), is a potent and useful clinical synthetic progestin for the treatment of menopausal complaints and is under current development for oral contraception. Previous studies in this laboratory demonstrated that NOMAC can block sulfatase and 17‚-hydroxysteroid dehydrogenase, the enzymes involved in the biosynthesis and transformation of estradiol (E2) in hormone- dependent MCF-7 and T-47D breast cancer cells. In the present study, the effect of NOMAC on sulfatase activity using total breast cancer tissue, compared to the effect in normal breast tissue, was explored. Slices of tumoral or normal breast tissues (45-65 mg) were incubated in buffer (20 mM Tris-HCl, pH 7.2) with physiological concentrations of ( 3 H)-estrone sulfate (5x10 -9 M), alone or in the presence of nomegestrol acetate (5x10 -5 - 5x10 -7 - 5x10 -9 M), for 4 h at 37AEC. Estrone sulfate (E1S), estrone (E1) and E2 were characterized by thin layer chromatography and quantified using the corresponding