|show drug details|
|20244-21-7 (unspecified hydrochloride salt)|
|4-06-00-05557 (Beilstein Handbook Reference)|
|C.I. Oxidation Base 26|
|catechol dipotassium salt|
|catechol sodium salt|
|catechol, 14C-labeled cpd|
|CI Oxidation Base 26|
|Durafur developer C|
|Durafur Developer CFouramine PCH|
|Pelagol Grey C|
|phenol derivative, 2|
|WLN: QR BQ|
|Ki: ||Kd:||Ic 50:||Ec50/Ic50:|
Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate.. S Garbisa; L Sartor; S Biggin; B Salvato; R Benelli; A Albini (2001) Cancer display abstract
BACKGROUND: Given the association of consumption of green tea with prevention of cancer development, metastasis, and angiogenesis, the effect of the main flavanol present, epigallocatechin-3-gallate (EGCG), on two gelatinases most frequently overexpressed in cancer and angiogenesis (MMP-2 and MMP-9) and on tumor cell invasion and chemotaxis were examined. METHODS: Zymography, Western blotting, and enzyme linked immuoadsorbent assay were used to analyze the effect of EGCG on MMP-2 and MMP-9 activity, whereas its effect on tumor cell invasion and chemotaxis was examined using modified Boyden chamber assays. RESULTS: A Zn2+ chelation-independent, dose-dependent, noncompetitive inhibition by EGCG of both gelatinases was found at concentrations 500 times lower than that reported to inhibit urokinase. Tumor cell invasion of a reconstituted basement membrane matrix, but not chemotaxis, was reduced by 50% with EGCG concentrations equivalent to that in the plasma of moderate green tea drinkers, and 2 orders of magnitude below those of tissue inhibitors of MMPs. Although higher concentrations of EGCG were associated with increased levels of both cell-associated gelatinases and their activator MT1-MMP, no increased gelatinase activation was found, and TIMP-1 and TIMP-2 inhibitors were up-regulated. Finally, concentrations of EGCG active in restraining proliferation and inducing apoptosis of transformed cells were more than 100 times lower than those reported for normal cells. CONCLUSIONS: Epigallocatechin-3-gallate is a potent inhibitor of gelatinases and an orally available pharmacologic agent that may confer the antiangiogenic and antimetastatic activity associated with green tea.
Green tea polyphenol (-)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells.. Borhane Annabi; Marie Paule Lachambre; Nathalie Bousquet-Gagnon; Martine Page; Denis Gingras; Richard Beliveau (2002) Biochimica et biophysica acta display abstract
We have recently shown that green tea polyphenols, and especially (-)-epigallocatechin 3-gallate (EGCg), acted as potent inhibitors of matrix metalloproteinase activities as well as of proMMP-2 activation (M. Demeule, M. Brossard, M. Page, D. Gingras, R. Beliveau, Biochim. Biophys. Acta 1478 (2000)). In the present work, we sought to examine the involvement of MT1-MMP in the EGCg-induced inhibition of proMMP-2 activation. The incubation of U-87 glioblastoma cells in the presence of concanavalin A or cytochalasin D, two potent activators of MT1-MMP, resulted in proMMP-2 activation that was correlated with the cell surface proteolytic processing of MT1-MMP to its inactive 43 kDa form. Addition of EGCg strongly inhibited the MT1-MMP-dependent proMMP-2 activation. The inhibitory effect of EGCg on MT1-MMP was also demonstrated by the down-regulation of MT1-MMP transcript levels and by the inhibition of MT1-MMP-driven cell migration of transfected COS-7 cells. These observations suggest that this catechin may act at both the MT1-MMP gene and protein expression levels. In addition, treatment of cells with non-cytotoxic doses of EGCg significantly reduced the amount of secreted proMMP-2, and led to a concomitant increase in intracellular levels of that protein. This effect was similar to that observed using well-characterized secretion inhibitors such as brefeldin A and manumycin, suggesting that EGCg could also potentially act on intracellular secretory pathways. Taken together, these results indicate that EGCg targets multiple MMP-mediated cellular events in cancer cells and provides a new mechanism for the anticancer properties of that molecule.
Association of suppression of extracellular signal-regulated kinase phosphorylation by epigallocatechin gallate with the reduction of matrix metalloproteinase activities in human fibrosarcoma HT1080 cells.. Mari Maeda-Yamamoto; Naoko Suzuki; Yoshinori Sawai; Toshio Miyase; Mitsuaki Sano; Akiko Hashimoto-Ohta; Mamoru Isemura (2003) Journal of agricultural and food chemistry display abstract
Matrix metalloproteinases (MMPs) play a crucial role in the process of cancer invasion and metastasis. Previous findings suggested that epigallocatechin gallate (EGCG), a main flavanol of green tea, caused decreased levels of MMP-2 and MMP-9 activities to be secreted into culture medium. To obtain further information on EGCG-mediated regulation of these MMPs, the effects of EGCG on enzyme activity, mRNA expression, and mitogen-activated protein kinase (MAPK) activities in human fibrosarcoma HT1080 cells were examined. EGCG was confirmed to suppress the gelatin-degrading activities due to MMP-2 and MMP-9 in the culture medium. This suppression of enzyme activities by EGCG was consistent with the decreased levels of MMP-2 and MMP-9 mRNAs. EGCG-mediated suppression was also observed for MT1-MMP mRNA. EGCG-mediated suppression of the level of MMP-9 transcript was correlated with its suppression of MMP-9 promoter activity. EGCG inhibited the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are the members of an MAPK family necessary for MMP-9 up-regulation. EGCG also suppressed p38 MAPK activity but gave no effects on stress-activated protein kinase/c-Jun N-terminal kinase activity. These findings suggest that suppression of ERK phosphorylation by EGCG is involved in the inhibition of expression for MMP-2 and MMP-9 mRNAs, leading to the reduction of their enzyme activities of the cancer cells. Methyl derivatives, epigallocatechin-3-O-(3-O-methyl) gallate and epigallocatechin-3-O-(4-O-methyl) gallate, exhibited effects similar to, but weaker than, those of EGCG, suggesting the important role of an unsubstituted triphenolic ester structure in these activities.
Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP.. Naoto Oku; Motomi Matsukawa; Satoru Yamakawa; Tomohiro Asai; Shoji Yahara; Fumio Hashimoto; Toshifumi Akizawa (2003) Biological & pharmaceutical bulletin display abstract
Matrix metalloproteinases (MMPs), especially membrane-type 1 matrix metalloproteinase (MT1-MMP), which generates an active form of MMP-2 from proMMP-2, are deeply involved in angiogenesis as well as in tumor cell migration and metastasis. To obtain a specific inhibitor for MT1-MMP, we screened a number of natural and synthetic compounds using recombinant human MMP-2, MMP-7, and soluble MT1-MMP in a fluorogenic peptide cleavage assay. (-)-Epigallocatechin 3-O-gallate (EGCG) followed by (-)-epigallocatechin 3,5-di-O-gallate and epitheaflagallin 3-O-gallate, was found to have potent and distinct inhibitory activity against MT1-MMP. Therefore, we investigated the effect of EGCG on the suppression of MMP-2 activation as determined by gelatin zymography, and observed that the active form of MMP-2 in the conditioned medium of human umbilical vein endothelial cells was decreased in the presence of EGCG. The results suggest the possibility that tea polyphenols suppress tumor growth through the suppression of angiogenesis.
Catechins prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression.. Jasser El Bedoui; Min-Ho Oak; Patrick Anglard; ValÚrie B Schini-Kerth (2005) Cardiovascular research display abstract
OBJECTIVE: Regular consumption of green tea is associated with a reduced risk of mortality due to coronary diseases and cancer. The present study examined whether a green tea extract (GTE) inhibits activation of matrix metalloproteinase-2 (MMP-2), a major collagenase involved in vascular remodeling of atherosclerotic plaques, in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: The expression of MMP-2 was assessed by Northern and Western blot analyses in human aortic VSMCs. MMP-2 activity was evaluated by zymography, membrane-type1-MMP (MT1-MMP, MMP-14) activity by an enzymatic assay, and cell invasion by a modified Boyden chamber assay. The thrombin-induced activation of secreted MMP-2 was abolished by GTE and the green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG). GTE reduced the expression of MMP-2 mRNA and protein. GTE, EGCG and ECG directly inhibited cell-associated MT1-MMP activity, the physiological activator of MMP-2, in a reversible manner. Thrombin-stimulated VSMCs invasion was abolished by EGCG and ECG, and reduced by GTE. CONCLUSIONS: GTE inhibits thrombin-induced VSMCs invasion most likely by preventing MMP-2 expression and its activation by a direct inhibition of MT1-MMP. The ability of green tea to prevent cell invasion and matrix degradation might contribute to its protective effect on atherosclerosis and cancer.
Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.. Triparna Sen; Shuvojit Moulik; Anindita Dutta; Paromita Roy Choudhury; Aniruddha Banerji; Shamik Das; Madhumita Roy; Amitava Chatterjee (2009) Life sciences display abstract
AIMS: The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7. MAIN METHODS: MCF-7 was treated with EGCG (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its regulatory molecules were studied by gelatin zymography, Western blot, quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell adhesion assay. KEY FINDINGS: EGCG treatment reduced the activity, protein expression and mRNA expression level of MMP-2. EGCG treatment reduced the expression of focal adhesion kinase (FAK), membrane type-1-matrix metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin and vitronectin. Real time RT-PCR revealed a reduced expression of integrin receptors alpha5, beta1, alphav and beta3 due to EGCG treatment. SIGNIFICANCE: Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of functional status of integrin receptors may indicate decreased MMP-2 activation; low levels of FAK expression might indicate disruption in FAK-induced MMP-2 secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K), extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2 regulation and induction. We propose EGCG as potential inhibitor of expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in MCF-7.