HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

The antitumor mechanism of progesterone antagonists is a receptor mediated antiproliferative effect by induction of terminal cell death.

Abstract
The antiprogesterones Onapristone, ZK 112.993 (Schering AG), and Mifepristone (Roussel-Uclaf) proved to possess progesterone receptor-mediated antiproliferative effects in experimental mammary carcinomas. In this study, the potency and mechanism of the antitumor action of Onapristone and ZK 112.993 is characterized by ovariectomized, progestagen and/or estradiol substituted mice bearing hormone-dependent MXT(+) mammary tumours. Medroxyprogesterone acetate (MPA, 0.8 mg/mouse, 3 times weekly, s.c.) could only induce a poor stimulation of tumour growth (% T/C = 40; intact control % T/C = 100), which was only marginally inhibited (% T/C = 21) by Onapristone (0.2 mg/mouse, 6 times weekly, s.c.) during a 6-week therapy. Therefore, the antitumor mechanism of antiprogesterones cannot preferably depend on a classical progesterone antagonism. In contrary, the pronounced stimulation of tumor growth (% T/C = 152) by estradiol benzoate (EB, 0.33 microgram/mouse, 3 times weekly, s.c.) was completely inhibited (% T/C = 7) by the antiprogesterones. An even more stimulated tumour growth was achieved by a combination of EB and MPA (% T/C = 365 using 0.17 mg; % T/C = 225 using 0.8 mg MPA). Onapristone dramatically blocked tumor growth (% T/C = 7) at the lower dose of MPA; no inhibition (% T/C = 203), however, was detected at the higher dose of MPA. These data and a morphological analysis indicate that the potent antitumor activity of the progesterone antagonists depends on the binding to a number of available progesterone receptors high enough to trigger an antiproliferative effect via the induction of terminal differentiation associated with terminal cell death.
AuthorsH Michna, M R Schneider, Y Nishino, M F el Etreby
JournalJournal of steroid biochemistry (J Steroid Biochem) Vol. 34 Issue 1-6 Pg. 447-53 ( 1989) ISSN: 0022-4731 [Print] ENGLAND
PMID2626038 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Gonanes
  • ZK 112993
  • Mifepristone
  • Progesterone
  • Estradiol
  • onapristone
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Cell Division (drug effects)
  • Cell Line
  • Cell Survival (drug effects)
  • Estradiol (pharmacology)
  • Female
  • Gonanes (therapeutic use)
  • Mammary Neoplasms, Experimental (drug therapy, pathology)
  • Mice
  • Mice, Inbred Strains
  • Mifepristone (analogs & derivatives, therapeutic use)
  • Ovariectomy
  • Progesterone (antagonists & inhibitors)
  • Tumor Cells, Cultured (cytology, drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: