Angiostatic activity of synthetic inhibitors of urokinase type plasminogen activator.
We hypothesize that tumor angiogenesis can be limited by the reduction of enzymatic activity of the urokinase type plasminogen activator. The proposed mechanism is elimination of proteolytic activity by the advancing tip of capillaries which utilize proteolysis to produce space needed for vessel expansion. To test our hypothesis, we have investigated the angiostatic activity of synthetic low molecular weight inhibitors of urokinase: amiloride, benzamidine, EGCG, B428, and B623 using the chicken embryo corioallantoic membrane (CAM) model. We found that all tested inhibitors of urokinase cause a significant reduction of angiogenesis.
Swiercz
R
R
Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, OH 43614-2589, USA.
Skrzypczak-Jankun
E
E
Merrell
M M
MM
Selman
S H
SH
Jankun
J
J
D000482:Allantois / Q000098:blood supply; D000578:Amidines / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
C097398:4-iodine-benzo(b)thiophene-2-carboxamidine; D000578:Amidines; C119100:B 623; D001550:Benzamidines; D004791:Enzyme Inhibitors; D015842:Serine Proteinase Inhibitors; D013876:Thiophenes; D000584:Amiloride; D002392:Catechin; C045651:epigallocatechin gallate; D014568:Urokinase-Type Plasminogen Activator; C032157:benzamidine