Possible Interaction: Urokinase-Type Plasminogen Activator and Epigallocatechin Gallate

“Urokinase (uPA) and tPA are activators of plasminogen, and uPA is inhibited by EGCG , but regardless of their structural similarity tPA is not inhibited.”

“Molecular modeling suggests that EGCG inhibits urokinase and matrix metalloproteinase-9.”

“… EGCG … urokinase (uPA), which plays a critical role in promoting cancer growth and metastasis.2 However, the most studied anticancer activity of EGCG was its ability … and MAPK activation8 and AKT inhibition.9 The potential use of EGCG as an anticancer reagent has attracted much attention in recent years.”

“On the other hand, EGCG at physiologically relevant concentration (1 microM) suppressed HGF-induced tumor motility and MMP-9 and uPA activities, and the suppression of Akt and Erk pathway by EGCG was one of the downstream mechanisms to facilitate EGCG-induced anti-invasion effects.”

“ EGCG was shown to block His 57 and Ser 195 of the uPA catalytic triad, thereby interfering with the ability of uPA to recognize its substrates (Jankun et al. 1997).”

“ EGCG was also found to decrease the expressions of MMP-2, MMP-9, and uPA in a concentration-dependent manner (P < 0.05).”

“Specifically, EGCG regulates expression of VEGF, matrix metalloproteinases, uPA , IGF-1, EGFR, cell cycle regulatory proteins and inhibits NFk B, PI3-K/Akt, Ras/Raf/MAPK and AP-1 signaling pathways, thereby causing strong cancer chemopreventive effects.”

“(-)-Epigallocatechin-3-gallate EGCG ), a main flavanol of green tea, potently suppressed the urokinase-type plasminogen activator (uPA) expression in human fibrosarcoma HT 1080 cells.”

“ EGCG induced not only the suppression of the uPA promoter activity but also the destabilization of uPA mRNA.”

“These results … that EGCG could … the uPA expression by at least two different mechanisms: EGCG may inhibit the Erk-1/2 and P38 MAPK, leading to suppression of the uPA promoter activity, and EGCG may destabilize the uPA mRNA in an Erk-1/2- and p38 MAPK-independent way.”

“Green tea polyphenols significantly decreased fluorescent … reported the inhibitory effect of EGCG … urokinase , a proteolytic enzyme necessary for invading tissue and/or metastasizing neoplastic cells, resulting in prevention of tumor growth … in increased apoptosis to 80.9% versus 1.5% in vehicle-treated cells as analyzed by flow cytometry.”

“Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity.”