Anti-angiogenic activity of a novel synthetic agent, 9alpha-fluoromedroxyprogesterone acetate

Cancer Lett. 1999 Oct 18;145(1-2):107-14. doi: 10.1016/s0304-3835(99)00239-6.

Abstract

9Alpha-fluoromedroxyprogesterone acetate (FMPA) is a novel synthetic analog of medroxyprogesterone acetate (MPA), widely used as therapeutic agent for breast and endometrium cancers. FMPA showed almost the same binding affinities to the progesterone and glucocorticoid receptors as MPA. In the rabbit corneal assay, FMPA, MPA and fumagillin significantly inhibited the angiogenic response induced by rat mammary tumor at doses of 0. 1, 1 and 50 microg/pellet, respectively, so FMPA showed greater anti-angiogenic activity than MPA and fumagillin. In the mouse dorsal air sac method, FMPA inhibited the mouse sarcoma 180 cell-induced angiogenesis by oral administration at a dose of 200 mg/kg. FMPA inhibited the activity of plasminogen activator (PA) in bovine endothelial cells. These results suggest that FMPA may be useful for diseases associated with angiogenesis by oral administration.

MeSH terms

  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Cattle
  • Cornea / drug effects*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Female
  • Mice
  • Progesterone / analogs & derivatives*
  • Progesterone / metabolism*
  • Progesterone / therapeutic use
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / metabolism*

Substances

  • 17-acetoxy-9-fluoro-6-methylprogesterone
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Receptors, Glucocorticoid
  • Progesterone