Medroxyprogesterone acetate, an anti-cancer and anti-angiogenic steroid, inhibits the plasminogen activator in bovine endothelial cells.
Medroxyprogesterone acetate (MPA) is an anti-cancer drug for mammary carcinomas and an angiostatic steroid. The effects of MPA on the growth and plasminogen activator (PA) activity of bovine endothelial cells were investigated to elucidate the inhibitory mechanism observed in angiogenesis. MPA did not suppress the growth of capillary endothelial cells, even at high concentrations. On the other hand, in bovine endothelial cells of 3 types (adrenal cortical capillary, aortic and pulmonary artery endothelial cells), MPA inhibited extracellular and cell-associated activity of PA, which might be a protease involved in the neovascular response. MPA also greatly inhibited the high level of PA induced by basic fibroblast growth factor (FGF). The same result was obtained when PA production was induced by 4 beta-phorbol-12-myristate-13-acetate (PMA) in endothelial cells. These findings suggest that one of the points of inhibitory action of MPA in the process of angiogenesis may be the suppression of PA activity, and that inhibition of this protease might be useful for reduction of tumorigenic or excessive angiogenesis in vivo.
Ashino-Fuse
H
H
Division of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Takano
Y
Y
Oikawa
T
T
Shimamura
M
M
Iwaguchi
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D066298:In Vitro Techniques; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D009389:Neovascularization, Pathologic; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D013997:Time Factors
D000970:Antineoplastic Agents; D015849:Plasminogen Inactivators; D005346:Fibroblast Growth Factors; D017258:Medroxyprogesterone Acetate; D010960:Plasminogen Activators; D008525:Medroxyprogesterone