Effect of Medrogestone on 17 beta-hydroxysteroid dehydrogenase activity inthe hormone-dependent MCF-7 and T-47D human breast cancer cell lines

Estradiol (E-2) is one of the most important hormones supporting the growth and evolution of breast cancer. Consequently, to block this hormone before it enters the cancer cell, or in the cell itself, has been one of the main targets in recent years. In the present study we explored the effect of Me drogestone (Prothil(u)) on 17 beta-hydroxysteroid dehydrogenase (17 beta-HS D) activities of the hormone-dependent MCF-7 and T-47D human breast cancer cell lines. Using physiological doses of estrone ([H-3]-E-1: 5 x 10(-9) mol /l) this estrogen is converted in a great proportion to E-2 in both cell li nes. After 24 h of the cell culture, Medrogestone significantly inhibits th is transformation in a dose-dependent manner by 39% and 80% at 5 x 10(-8) M and 5 x 10(-5) M, respectively in T-47D cells. the effect is less intense in MCF-7 cells: 25% and 55% respectively. The IC50 values are 0.45 mu mol/l in T-47D and 17.36 mu mol/l in MCF-7 cells. It is concluded that the inhibition provoked by Medrogestone on the reducti ve 17 beta-HSD activity involved in the local biosynthesis of the biologica lly active estrogen estradiol, may constitute a new therapeutic approach fo r the treatment of breast cancer. (C) 1999 Published by Elsevier Science Lt d. All rights reserved.