EFFECT OF NOMEGESTROL ACETATE ON ESTRONE-SULFATASE AND 17-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITIES IN HUMAN BREAST-CANCER CELLS

It is well. recognized that estradiol (E(2)) is one of the most import ant hormones supporting the growth and evolution of breast cancer. Con sequently, to block this hormone before it enters the cancer cell or i n the cell, itself, has been one of the main targets in recent years. In the present study we explored the effect of the progestin, nomegest rol acetate, on the estrone sulfatase and 17 beta-hydroxysteroid dehyd rogenase (17 beta-HSD) activities of MCF-7 and T-47D human breast canc er cells. Using physiological doses of estrone sulfate (E(1)S: 5 x 10( -9) M), nomegestrol acetate blocked very significantly the conversion of E(1)S to E(2) In the MCF-7 cells, using concentrations of 5 x 10(-6 ) M and 5 x 10(-5) M of nomegestrol acetate, the decrease of E(1)S to E(2) was, respectively, -43% and -77%. The values were, respectively, -60% and -71% for the T-47D cells. Using E(1)S at 2 x 10(-6) M and nom egestrol acetate at 10(-5) M, a direct inhibitory effect on the enzyme of -36% and -18% was obtained with the cell homogenate of the MCF-7 a nd T-47D cells, respectively. In another series of studies, it was obs erved that after 24 h incubation of a physiological concentration of e strone (E(1): 5 x 10(-9) M) this estrogen is converted in a great prop ortion to E(2). Nomegestrol acetate inhibits this transformation by -3 5% and -85% at 5 x 10(-7) M and 5 x 10(-5) M, respectively in T-47D ce lls; whereas in the MCF-7 cells the inhibitory effect is only signific ant, -48%, at 5 x 10(-5) M concentration of nomegestrol acetate. It is concluded that nomegestrol acetate in the hormone-dependent MCF-7 and T-47D breast cancer cells significantly inhibits the estrone sulfatas e and 17B-HSD activities which converts E(1)S to the biologically acti ve estrogen estradiol. This inhibition provoked by this progestin on t he enzymes involved in the biosynthesis of E(2) can open new clinical possibilities in breast cancer therapy. Copyright (C) 1996 Elsevier Sc ience Ltd.