Effect of Medrogestone on 17beta-hydroxysteroid dehydrogenase activity in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines.
Estradiol (E2) 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 Medrogestone (Prothil) on 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities of the hormone-dependent MCF-7 and T-47D human breast cancer cell lines. Using physiological doses of estrone ([3H]-E1: 5 x 10(-9) mol/l) this estrogen is converted in a great proportion to E2 in both cell lines. After 24 h of the cell culture, Medrogestone significantly inhibits this 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 micromol/l in T-47D and 17.36 micromol/l in MCF-7 cells. It is concluded that the inhibition provoked by Medrogestone on the reductive 17beta-HSD activity involved in the local biosynthesis of the biologically active estrogen estradiol, may constitute a new therapeutic approach for the treatment of breast cancer.
Chetrite
G S
GS
Steroid Hormone Research Unit, Institut de Puériculture, Paris, France.
Ebert
C
C
Wright
F
F
Philippe
J C
JC
Pasqualini
J R
JR
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis; D004970:Estrone / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008524:Medrogestone / Q000008:administration & dosage / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D008524:Medrogestone; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases