|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.
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.
Repressions of MMP-9 expression and NF-kappa B localization are involved in inhibition of lung carcinoma 95-D cell invasion by (-)-epigallocatechin-3-gallate.. Jingya Yang; Dongzhi Wei; Jianwen Liu (2005) Biomedicine & pharmacotherapy display abstract
Epigallocatechin-3-gallate (EGCG) repressed the invasion of lung carcinoma 95-D cells in invasion assay. RT-PCR analysis illuminated that 40 microM EGCG down-regulated the expression of MMP-9 by 45.7% and the result of Western blot analysis provided further evidence. NF-kappa B localized in the nucleus of the 95-D cells was diminished in a dose-dependent manner in EGCG-treated cells as shown by Western blot. Intracellular oxidants were more abundant in invasive cells than in invasion-suppressed cells fed with EGCG for 18 h. Thus, the inhibition of tumor invasion by EGCG was shown to be attributed to decreases of the expression of MMP-9 and NF-kappa B, which may result from decrease of intracellular oxidants.