Urokinase-plasminogen activator inhibition

Ho YC, Yang SF, Peng CY, Chou MY, Chang YC. 2007. Epigallocatechin-3-gallate inhibits the invasion of human oral cancer cells and decreases the productions of matrix metalloproteinases and urokinase-plasminogen activator. J Oral Pathol Med 36 588-593. 

Slivova V, Zaloga G, DeMichele SJ, Mukerji P, Huang YS, Siddiqui R, Harvey K, Valachovicova T, Sliva D. 2005. Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells. Nutr Cancer 52 66-73. 

E9. Evans, C. P., Elfman, F., Parangi, S., Conn, M., Cunha, G., and Shuman, M. A., Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade. Cancer Res. 57, 3594-3599 (1997). 

Hansen M, et al. A urokinase-type plasminogen activator-inhibiting cyclic peptide widi an unusual P2 residue and an extended protease binding surface demonstrates new modalities for enzyme inhibition. J. Biol. Chem. 2005 280 38424-38437. 

Pulukuri SM, Rao JS. Small interfering RNA directed reversal of urokinase plasminogen activator demethylation inhibits prostate tumor growth and metastasis. Cancer Res 2007 67 6637 646. 

Shan et al. found two significantly inhibited tumor invasions and metastasis in CRC cell lines HT29 and SW480 in vivo (0-80 mg/kg/day for 4 weeks). The results revealed that Tan-IIA showed the activity by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9 and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-l... 

Plasminogen activator inhibitors have been shown to be present in a large variety of different cells and tissues. These inhibitors are thought to play an important role in regulating tissue fibrinolysis. One of these inhibitors has been purified from cultured bovine aortic epithelial cells. This inhibitor has been shown to be a serine protease inhibitor and inhibits the function of two proteolytic enzymes urokinase and tissue plasminogen activator, both of which cleave and activate plasminogen. The mechanism by which this inhibitor functions is very similar to that described above with a-l-PI. Thus, the inhibitor forms a binary complex with the proteolytic enzyme and thereby inhibits its activity. Again in a situation comparable to that with a-l-PI, it was found that when the purified bovine aortic epithelial inhibitor was exposed to Al-chlorosuccinimide,... 

Reboud-Ravaux, M. Desvages, G. Chapeville, F. Irreversible inhibition and peptide mapping of urinary plasminogen activator urokinase. FEBS Lett 1982, 140, 58-62. 

Lottenberg R., Sjak-Shie N., Fazleabas A. T Roberts R. M. Aprotinin inhibits urokinase but not tissue-type plasminogen activator. Thromb Res 1988 49,549-56. 

Ossowski, L., Russo-Payne, H., and Wilson, E. L., Inhibition of urokinase-type plasminogen activator by antibodies The effect on dissemination of a human tumor in the nude mouse model. Cancer Res. 51, 274-281 (1991). 

The fibrin thrombus resulting from blood clotting (see p. 290) is dissolved again by plasmin, a serine proteinase found in the blood plasma. For this purpose, the precursor plasminogen first has to be proteolyti-cally activated by enzymes from various tissues. This group includes the plasminogen activator from the kidney (urokinase) and tissue plasminogen activator (t-PA) from vascular endothelia. By contrast, the plasma protein a2-antiplasmin, which binds to active plasmin and thereby inactivates it, inhibits fibrinolysis. 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

SR023 Ishii, K., S. Usui, Y. Sugimura, H. Yamamoto, K. Yoshikawa, and K. Hiran. Extract from Serenoa repens suppresses the invasion activity of human urological cancer cells by inhibiting urokinase-type plasminogen activator. Biol Pharm Bull 2001 24(2) 188-190. 

Aminocaproic acid inhibits urokinase-induced activation of plasminogen (see Figure 45). 

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