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| Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin.
EGCG – the most abundant catechin in tea – is a polyphenol under basic research for its potential to affect human health and disease. EGCG is used in many dietary supplements. |
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Read full article at Wikipedia
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InChI=1S/C22H18O11/c23- 10-5-12(24)11-7-18(33-22(31)9-3-15(27)20(30)16(28)4-9)21(32-17(11)6-10)8-1-13(25)19(29)14(26)2-8/h1-6,18,21,23-30H,7H2/t18-,21-/m1/s1 |
| WMBWREPUVVBILR-WIYYLYMNSA-N |
| OC1=CC(O)=C2C[C@@H](OC(=O)C3=CC(O)=C(O)C(O)=C3)[C@H](OC2=C1)C1=CC(O)=C(O)C(O)=C1 |
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Parapiptadenia rigida
(NCBI:txid148713)
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Found in
bark
(BTO:0001301).
Ethanolic extract of air-dried, powdered bark
See:
PubMed
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Camellia sinensis
(NCBI:txid4442)
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See:
PubMed
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Camellia sinensis
(NCBI:txid4442)
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From MetaboLights
See:
MetaboLights Study
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antioxidant
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
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plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
Hsp90 inhibitor
An EC 3.6.4.10 (non-chaperonin molecular chaperone ATPase) inhibitor that blocks the action of heat shock protein 90.
apoptosis inducer
Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
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antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
geroprotector
Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
neuroprotective agent
Any compound that can be used for the treatment of neurodegenerative disorders.
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View more via ChEBI Ontology
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(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
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(−)-epigallocatechin 3-O-gallate
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ChEBI
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(−)-epigallocatechin gallate
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ChemIDplus
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(−)-epigallocatechin-3-O-gallate
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ChemIDplus
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(−)-epigallocatechol gallate
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ChemIDplus
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3-O-galloyl-(−)-epigallocatechin
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ChEBI
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[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate
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ChEBI
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EGCG
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ChemIDplus
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epigallocatechin 3-gallate
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KEGG COMPOUND
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epigallocatechin 3-O-gallate
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ChEBI
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epigallocatechin gallate
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ChemIDplus
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L-epigallocatechin gallate
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ChemIDplus
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NVP-XAA 723
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ChemIDplus
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3658838
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Beilstein Registry Number
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Beilstein
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67944
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Reaxys Registry Number
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Reaxys
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989-51-5
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CAS Registry Number
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KEGG COMPOUND
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989-51-5
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CAS Registry Number
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ChemIDplus
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Suihara S, Ishisaka A, Murakami A (2021)
(-)-Epigallocatechin-3-O-gallate at a high concentration may induce lipolysis via ATP consumption by activation of stress defense mechanisms.
Bioscience, biotechnology, and biochemistry 85, 411-420 [PubMed:33604623]
[show Abstract]
Green tea catechins have thus far been demonstrated to have antiobesity effects in a variety of experimental models. However, upstream molecular events triggering those phenomena remain to be identified. In this study, we found that (-)-epigallocatechin-3-O-gallate (EGCG) promoted lipolysis in lipid-loaded Huh7 human hepatoma cells. Notably, EGCG at a high concentration induced both oxidative stress and protein stress (proteo-stress), leading to activation of stress defense mechanisms, such as mRNA expressions of antioxidant and phase-2 detoxifying enzymes, and heat shock proteins. Furthermore, EGCG decreased the level of intracellular ATP, while glucose uptake from culture media was promoted possibly for energy homeostasis. EGCG also upregulated the expression of adipose triglyceride lipase, and activated AMP-activated protein kinase. Collectively, these results suggest that EGCG induces lipolysis to compensate for ATP reduction derived from activation of stress defense systems against its oxidative and proteo-stress properties. | Jiang C, Wang L, Huang X, Zhu S, Ma C, Wang H (2021)
Structural characterization and antioxidant property of enzymatic-transesterification derivatives of (-)-epigallocatechin-3-O-gallate and vinyl laurate.
Journal of food science 86, 4717-4729 [PubMed:34553787]
[show Abstract]
(-)-Epigallocatechin-3-O-gallate(EGCG) was enzymatically modified to enhance the lipophilicity and the antioxidant property. The determination of optimal reaction conditions are as follows: Lipase DF "Amano" 15 and acetone were used as catalyst and solvent, respectively. Equal molar of EGCG and vinyl laurate (1:1); lipase addition of 6.0% (w/w of total substrates); reaction temperature of 50°C and reaction time of 96 h, which obtained the conversion rate of EGCG at 80.1%. The structure of EGCG lauroyl derivatives were 5″-O-lauroyl-EGCG, 3″,5″-2-O-lauroyl-EGCG, and 5',3″,5″-3-O-lauroyl-EGCG, identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR). Compared with the logP of precursor EGCG (0.69 ± 0.03), the logP of EGCG lauroyl derivatives was 1.37 ± 0.19, 2.27 ± 0.33, and 3.28 ± 0.37, increasing by 0.98, 2.28, and 3.75 times, respectively (p < 0.05), suggesting the grafted fatty acid chains make EGCG derivatives more lipophilic, and the lipid solubility gradually increased as the number of substituents increased. Furthermore, EGCG lauroyl derivatives had excellent lipid oxidation than that of EGCG. The POVs (peroxide values) of soybean oil with mono-, di-, tri-lauroyl EGCG were significantly reduced by 42%, 47%, and 57% than that of EGCG at 21 days, respectively, indicating the antioxidative inhibition of these derivatives decreased with the increase in substituents. This indicates that these derivatives have broad prospects of the antioxidant application while improving their solubility properties in lipophilic environments/high-fat food. Practical Application: The lipophilic esterification reaction of EGCG catalyzed by new catalytic lipase DF "Amano" 15 was carried out in a non-aqueous solvent.Various reaction factors on a higher conversion rate of EGCG lauroyl derivatives were evaluated. The lipophilicity and antioxidant properties of EGCG lauroyl derivatives were much excellent than that of parent EGCG. | Piwowarczyk L, Stawny M, Mlynarczyk DT, Muszalska-Kolos I, Goslinski T, Jelińska A (2020)
Role of Curcumin and (-)-Epigallocatechin-3-O-Gallate in Bladder Cancer Treatment: A Review.
Cancers 12, E1801 [PubMed:32635637]
[show Abstract]
The incidence of bladder cancer (BC) is increasing, and although current therapeutic approaches are effective in many cases, recurrence of BC is common. Therefore, it seems necessary to search not only for novel therapeutic approaches, but also for new therapeutic agents. Natural polyphenols, such as curcumin (CUR) and epigallocatechin gallate (EGCG), possess remarkable antitumor activity. Their biochemical mechanisms of action include regulation of signaling pathways, modeling of proteins involved in apoptosis and cell cycle inhibition, angiogenesis, and the proliferation, migration and adhesion of tumor cells. Both compounds also present antioxidant, anti-inflammatory, antibacterial and antiviral properties. CUR has been considered a promising candidate for the treatment of cystic fibrosis, Alzheimer's disease or malaria, whereas EGCG can play a supportive role in the treatment of obesity, metabolic and neurodegenerative diseases. The review summarizes the latest research on the role of CUR and EGCG in the treatment of BC. In particular, the effects of CUR and EGCG, and their prospects for use in BC therapy, their inhibition of cancer development and their prevention of multidrug resistance, are described. The literature's data indicate the possibility of achieving the effect of synergism of both polyphenols in BC therapy, which has been observed so far in the treatment of ovarian, breast and prostate cancer. | Ishizu T (2020)
Development of High-Order Functions Using (-)-Epigallocatechin-3-O-gallate in Water.
Chemical & pharmaceutical bulletin 68, 1143-1154 [PubMed:33268646]
[show Abstract]
The high-order functions of molecular capture and chiral recognition of tea gallated catechins (-)-epigallocatechin-3-O-gallate (EGCg) in water were investigated. A solution of equimolar amounts of a variety of heterocyclic compounds and EGCg in water afforded adhesive precipitates containing the heterocyclic compounds and EGCg at a molar ratio of 1 : 1, based on the integrated value of NMR proton signals. The molecular capture abilities of a variety of heterocyclic compounds using EGCg from the aqueous solutions were evaluated with the ratios of the heterocyclic compounds included in the precipitates of EGCg complex to the total heterocyclic compounds used. In the 1H-NMR spectrum of a solution containing cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), and EGCg in a D2O solution, a difference in the chemical shift of the 1H-NMR signal for some protons of the Pro residue was observed. Judging from the crystal structures of the 2 : 2 EGCg complexes of cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), the difference in the chemical shift derived mainly from a magnetic anisotropic shielding effect by the ring current from the B ring of EGCg.In the 1H-NMR spectrum of a solution containing the pharmaceuticals racemic (R,S)-propranolol, (R,S)-diprophylline, (R,S)-proxyphylline and EGCg in D2O, splitting of the 1H-NMR signals of the pharmaceuticals was observed. It was suggested that the pharmaceuticals formed diastereomers of EGCg complexes, as a result chirality of the pharmaceuticals was recognized by EGCg in the D2O solution. | Inacio JDF, Fonseca MS, Almeida-Amaral EE (2019)
(-)-Epigallocatechin 3-O-Gallate as a New Approach for the Treatment of Visceral Leishmaniasis.
Journal of natural products 82, 2664-2667 [PubMed:31503486]
[show Abstract]
In addition to generating side effects and resistance, treatment for visceral leishmaniasis remains mostly ineffective and expensive, and it has a long duration. Thus, natural products are an important alternative for treatment of the disease. In this study, we demonstrate the in vitro and in vivo activity of (-)-epigallocatechin 3-O-gallate (1) against Leishmania infantum. Compound 1 reduced the infection index with an EC50 value of 2.6 μM. Oral administration of 1 on L. infantum-infected BALB/c mice was capable to reduce the liver-parasite load with a ED50 and ED90 value of 12.4 and 21.5 mg/kg/day, respectively. Together, the results demonstrated 1 as a new compound for the treatment of visceral leishmaniasis. | Ramirez-Escudero M, Miguez N, Gimeno-Perez M, Ballesteros AO, Fernandez-Lobato M, Plou FJ, Sanz-Aparicio J (2019)
Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous.
Scientific reports 9, 17441 [PubMed:31767902]
[show Abstract]
Enzymatic glycosylation of polyphenols is a tool to improve their physicochemical properties and bioavailability. On the other hand, glycosidic enzymes can be inhibited by phenolic compounds. In this work, we studied the specificity of various phenolics (hydroquinone, hydroxytyrosol, epigallocatechin gallate, catechol and p-nitrophenol) as fructosyl acceptors or inhibitors of the β-fructofuranosidase from Xanthophyllomyces dendrorhous (pXd-INV). Only hydroquinone and hydroxytyrosol gave rise to the formation of glycosylated products. For the rest, an inhibitory effect on both the hydrolytic (H) and transglycosylation (T) activity of pXd-INV, as well as an increase in the H/T ratio, was observed. To disclose the binding mode of each compound and elucidate the molecular features determining its acceptor or inhibitor behaviour, ternary complexes of the inactive mutant pXd-INV-D80A with fructose and the different polyphenols were analyzed by X-ray crystallography. All the compounds bind by stacking against Trp105 and locate one of their phenolic hydroxyls making a polar linkage to the fructose O2 at 3.6-3.8 Å from the C2, which could enable the ulterior nucleophilic attack leading to transfructosylation. Binding of hydroquinone was further investigated by soaking in absence of fructose, showing a flexible site that likely allows productive motion of the intermediates. Therefore, the acceptor capacity of the different polyphenols seems mediated by their ability to make flexible polar links with the protein, this flexibility being essential for the transfructosylation reaction to proceed. Finally, the binding affinity of the phenolic compounds was explained based on the two sites previously reported for pXd-INV. | Niu Y, Na L, Feng R, Gong L, Zhao Y, Li Q, Li Y, Sun C (2013)
The phytochemical, EGCG, extends lifespan by reducing liver and kidney function damage and improving age-associated inflammation and oxidative stress in healthy rats.
Aging cell 12, 1041-1049 [PubMed:23834676]
[show Abstract]
It is known that phytochemicals have many potential health benefits in humans. The aim of this study was to investigate the effects of long-term consumption of the phytochemical, epigallocatechin gallate (EGCG), on body growth, disease protection, and lifespan in healthy rats. 68 male weaning Wistar rats were randomly divided into the control and EGCG groups. Variables influencing lifespan such as blood pressure, serum glucose and lipids, inflammation, and oxidative stress were dynamically determined from weaning to death. The median lifespan of controls was 92.5 weeks. EGCG increased median lifespan to 105.0 weeks and delayed death by approximately 8-12 weeks. Blood pressure and serum glucose and lipids significantly increased with age in both groups compared with the levels at 0 week. However, there were no differences in these variables between the two groups during the whole lifespan. Inflammation and oxidative stress significantly increased with age in both groups compared with 0 week and were significantly lower in serum and liver and kidney tissues in the EGCG group. Damage to liver and kidney function was significantly alleviated in the EGCG group. In addition, EGCG decreased the mRNA and protein expressions of transcription factor NF-κB and increased the upstream protein expressions of silent mating type information regulation two homolog one (SIRT1) and forkhead box class O 3a (FOXO3a). In conclusion, EGCG extends lifespan in healthy rats by reducing liver and kidney damage and improving age-associated inflammation and oxidative stress through the inhibition of NF-κB signaling by activating the longevity factors FoxO3a and SIRT1. | Lopez del Amo JM, Fink U, Dasari M, Grelle G, Wanker EE, Bieschke J, Reif B (2012)
Structural properties of EGCG-induced, nontoxic Alzheimer's disease Aβ oligomers.
Journal of molecular biology 421, 517-524 [PubMed:22300765]
[show Abstract]
The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease β-amyloid peptide (Aβ) neurotoxicity. Solution-state NMR allows probing initial EGCG-Aβ interactions. We show that EGCG-induced Aβ oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of Aβ. The C-terminal part of the Aβ peptide (residues 22-39) adopts a β-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Aβ aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development. | Kowalinski E, Zubieta C, Wolkerstorfer A, Szolar OH, Ruigrok RW, Cusack S (2012)
Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase.
PLoS pathogens 8, e1002831 [PubMed:22876177]
[show Abstract]
It is generally recognised that novel antiviral drugs, less prone to resistance, would be a desirable alternative to current drug options in order to be able to treat potentially serious influenza infections. The viral polymerase, which performs transcription and replication of the RNA genome, is an attractive target for antiviral drugs since potent polymerase inhibitors could directly stop viral replication at an early stage. Recent structural studies on functional domains of the heterotrimeric polymerase, which comprises subunits PA, PB1 and PB2, open the way to a structure based approach to optimise inhibitors of viral replication. In particular, the unique cap-snatching mechanism of viral transcription can be inhibited by targeting either the PB2 cap-binding or PA endonuclease domains. Here we describe high resolution X-ray co-crystal structures of the 2009 pandemic H1N1 (pH1N1) PA endonuclease domain with a series of specific inhibitors, including four diketo compounds and a green tea catechin, all of which chelate the two critical manganese ions in the active site of the enzyme. Comparison of the binding mode of the different compounds and that of a mononucleotide phosphate highlights, firstly, how different substituent groups on the basic metal binding scaffold can be orientated to bind in distinct sub-pockets within the active site cavity, and secondly, the plasticity of certain structural elements of the active site cavity, which result in induced fit binding. These results will be important in optimising the design of more potent inhibitors targeting the cap-snatching endonuclease activity of influenza virus polymerase. | Urusova DV, Shim JH, Kim DJ, Jung SK, Zykova TA, Carper A, Bode AM, Dong Z (2011)
Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1.
Cancer prevention research (Philadelphia, Pa.) 4, 1366-1377 [PubMed:21750208]
[show Abstract]
The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate-induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1. | Hazawa M, Takahashi K, Sugata S, Kashiwakura I (2011)
(-)-Epigallocatechin-3-O-gallate induces nonapoptotic cell death in leukemia cells independent of the 67 kDa laminin receptor.
Journal of natural products 74, 695-700 [PubMed:21434603]
[show Abstract]
The 67 kDa laminin receptor (67 LR) mediates (-)-epigallocatechin-3-O-gallate (1; EGCG)-67 LR direct action only at physiological concentrations. The relevancy of biological effects of 1 at physiological concentrations to 67 LR was investigated in myeloid and lymphoid leukemia cells using flow cytometric analysis. It was shown that physiological concentrations of 1 suppressed the cell growth of HL60 myeloid leukemia cells and Raji lymphoid leukemic cells independent of 67 LR expression. Moreover, there was no discernible change in the levels of intracellular reactive oxygen species, characteristics of apoptosis such as phosphatidylserine translocation and activated caspase-3. The activity of 1 at physiological concentrations does not depend on direct 67 LR-mediated actions, and this compound induces necrosis-like death of promyelocytic leukemia and non-Hodgkin's lymphoma cells. | Miyata M, Sato T, Kugimiya M, Sho M, Nakamura T, Ikemizu S, Chirifu M, Mizuguchi M, Nabeshima Y, Suwa Y, Morioka H, Arimori T, Suico MA, Shuto T, Sako Y, Momohara M, Koga T, Morino-Koga S, Yamagata Y, Kai H (2010)
The crystal structure of the green tea polyphenol (-)-epigallocatechin gallate-transthyretin complex reveals a novel binding site distinct from the thyroxine binding site.
Biochemistry 49, 6104-6114 [PubMed:20565072]
[show Abstract]
Amyloid fibril formation is associated with protein misfolding disorders, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Familial amyloid polyneuropathy (FAP) is a hereditary disease caused by a point mutation of the human plasma protein, transthyretin (TTR), which binds and transports thyroxine (T(4)). TTR variants contribute to the pathogenesis of amyloidosis by forming amyloid fibrils in the extracellular environment. A recent report showed that epigallocatechin 3-gallate (EGCG), the major polyphenol component of green tea, binds to TTR and suppresses TTR amyloid fibril formation. However, structural analysis of EGCG binding to TTR has not yet been conducted. Here we first investigated the crystal structure of the EGCG-V30M TTR complex and found novel binding sites distinct from the thyroxine binding site, suggesting that EGCG has a mode of action different from those of previous chemical compounds that were shown to bind and stabilize the TTR tetramer structure. Furthermore, EGCG induced the oligomerization and monomer suppression in the cellular system of clinically reported TTR variants. Taken together, these findings suggest the possibility that EGCG may be a candidate compound for FAP therapy. | Cheng CW, Shieh PC, Lin YC, Chen YJ, Lin YH, Kuo DH, Liu JY, Kao JY, Kao MC, Way TD (2010)
Indoleamine 2,3-dioxygenase, an immunomodulatory protein, is suppressed by (-)-epigallocatechin-3-gallate via blocking of gamma-interferon-induced JAK-PKC-delta-STAT1 signaling in human oral cancer cells.
Journal of agricultural and food chemistry 58, 887-894 [PubMed:19928918]
[show Abstract]
Immune escape is a characteristic of cancer progression, but its underlying molecular mechanism is still poorly understood. An immunomodulatory protein, indoleamide 2,3-dioxygenase (IDO), is induced by gamma-interferon (IFN-gamma) in several immune cells; those cells are observed in cancer cell microenvironment and can enhance immune escape. Previous studies show that IDO is expressed in the process of tumor formation and associated with cancer cell immune tolerance. By locally degrading tryptophan, IDO inhibits the proliferation of T lymphocytes and induces T cell apoptosis, leading to suppression of T cell response. In this study, (-)-epigallocatechin-3-gallate (EGCG), the major constituent of green tea, is found to significantly inhibit the expression of IDO in human oral cancer cell lines. EGCG suppresses the induction of IDO at transcriptional level. Activation of STAT1 is discovered to play an important role in regulating IDO expression by IFN-gamma. The study results demonstrate that EGCG can inhibit translocation of STAT1 into nucleus in IFN-gamma-stimulated human oral cancer cells. In addition, both tyrosine and serine phosphorylation of STAT1 are revealed to be suppressed by EGCG. Moreover, phosphorylation of PKC-delta, JAK-1, and JAK-2, which are the upstream event for the activation of STAT1, are also inhibited by EGCG in IFN-gamma-stimulated human oral cancer cells. These data show that EGCG inhibited IDO expression by blocking the IFN-gamma-induced JAK-PKC-delta-STAT1 signaling pathway. This study indicates that EGCG is a potential drug for immune and target therapy to enhance cancer therapy by increasing antitumor immunity. | Schmidt CA, Murillo R, Bruhn T, Bringmann G, Goettert M, Heinzmann B, Brecht V, Laufer SA, Merfort I (2010)
Catechin derivatives from Parapiptadenia rigida with in vitro wound-healing properties.
Journal of natural products 73, 2035-2041 [PubMed:21080642]
[show Abstract]
Analysis of the ethanolic extract of the bark from Parapiptadenia rigida resulted in the isolation of the new catechin derivatives 4',3''-di-O-methylapocynin-D (10), 4',3''-di-O-methylapocynin-B (11), epigallocatechin-3-O-ferulate (8), and 4'-O-methylepigallocatechin-3-O-ferulate (9) and the catechins 4'-O-methylepigallocatechin-3-O-gallate (6) and 4'-O-methylepicatechin-3-O-gallate (7). These compounds, isolated for the first time from a natural source, are accompanied by the five known catechins 4'-O-methylgallocatechin (1), 4'-O-methylepigallocatechin (2), 3'-O-methylepicatechin (3), epigallocatechin-3-O-gallate (4), and epicatechin-3-O-gallate (5). Compounds 5 and 7 displayed promising wound-healing effects in a scratch assay. Some of the catechin derivatives showed inhibitory effects on NF-κB DNA binding and p38α MAPK activity. | Qiao Y, Cao J, Xie L, Shi X (2009)
Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells.
Archives of pharmacal research 32, 1309-1315 [PubMed:19784588]
[show Abstract]
EGCG [(-)-epigallocatechin-3-gallate] has shown its antitumor ability and perhaps a potential regimen for cancer patients. The goal of this study was to investigate the effect of EGCG on human papilloma virus (HPV) positive cervical cancer cell lines. EGCG inhibited the growth of CaSki (HPV16 positive) and HeLa (HPV18 positive) cells in a time- and concentration-dependent manner. Cell cycle arrest and apoptosis were observed in two cell lines after EGCG exposure. More importantly, we focused on EGCG regulation ability on pivotal genes involved in cervical cancer: viral oncogenes E6/E7, estrogen receptor (ER) and aromatase. Our results suggested that EGCG may be suitable for prevention and treatment of cervical cancer. | Ochiai H, Takeda K, Soeda S, Tahara Y, Takenaka H, Abe K, Hayashi Y, Noguchi S, Inoue M, Schwarz S, Schwarz W, Kawamura M (2009)
Epigallocatechin-3-gallate is an inhibitor of Na+, K(+)-ATPase by favoring the E1 conformation.
Biochemical pharmacology 78, 1069-1074 [PubMed:19539611]
[show Abstract]
Four catechins, epigallocatechin-3-gallate, epigallocatechin, epicatechin-3-gallate, and epicatechin, inhibited activity of the Na(+),K(+)-ATPase. The two galloyl-type catechins were more potent inhibitors, with IC(50) values of about 1 microM, than were the other two catechins. Inhibition by epigallocatechin-3-gallate was noncompetitive with respect to ATP. Epigallocatechin-3-gallate reduced the affinity of vanadate, shifted the equilibrium of E1P and E2P toward E(1)P, and reduced the rate of the E1P to E2P transition. Epigallocatechin-3-gallate potently inhibited membrane-embedded P-type ATPases (gastric H+, K(+)-ATPase and sarcoplasmic reticulum Ca(2+)-ATPase) as well as the Na(+),K(+)-ATPase, whereas soluble ATPases (bacterial F(1)-ATPase and myosin ATPase) were weakly inhibited. Solubilization of the Na(+),K(+)-ATPase with a nonionic detergent reduced sensitivity to epigallocatechin-3-gallate with an elevation of IC50 to 10 microM. These results suggest that epigallocatechin-3-gallate exerts its inhibitory effect through interaction with plasma membrane phospholipid. | Yin Z, Henry EC, Gasiewicz TA (2009)
(-)-Epigallocatechin-3-gallate is a novel Hsp90 inhibitor.
Biochemistry 48, 336-345 [PubMed:19113837]
[show Abstract]
(-)-Epigallocatechin-3-gallate (EGCG), a major component of green tea, protects against certain types of cancers, although the mechanism has not yet been determined. It was previously demonstrated that EGCG blocks aryl hydrocarbon receptor (AhR)-mediated transcription induced by the potent carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Unlike other AhR antagonists that directly bind to the AhR, EGCG inhibits AhR-mediated transcription by binding to hsp90. We hypothesize that EGCG exerts anti-AhR and anticancer effects by acting as an hsp90 inhibitor. Using proteolytic footprinting, immunoprecipitation, and an ATP-agarose pull-down assay, EGCG was found to directly modulate the conformation of hsp90 and bind at or near to a C-terminal ATP binding site. Hsp90 chaperone function, as assessed by its ability to mediate refolding of denatured luciferase, was inhibited by EGCG treatment. Hsp90 dimerization, which occurs at the C-terminal end, was also inhibited by EGCG treatment. Coimmunoprecipitation studies showed that EGCG stabilizes an AhR complex that includes hsp90 and XAP2 (hepatitis B virus X-associated protein 2), and decreases the association of aryl hydrocarbon nuclear translocator (Arnt) with ligand-activated AhR. Thus, EGCG, through its ability to bind to hsp90, blocks AhR response element (AhRE) recognition. These studies indicate a novel mechanism whereby EGCG inhibits ligand-induced AhRE binding and AhR-mediated transcriptional activity. In EGCG-treated human ovarian carcinoma SKOV3 cells, decreased levels of several cancer-related hsp90 client proteins, such as ErbB2, Raf-1 and phospho-AKT, were observed. EGCG also modified the association of hsp90 with several cochaperones. Overall, these data indicate that EGCG is a novel hsp90 inhibitor. Further studies are needed to determine if this has a role in the antitumor actions of EGCG. | Abbas S, Wink M (2009)
Epigallocatechin gallate from green tea (Camellia sinensis) increases lifespan and stress resistance in Caenorhabditis elegans.
Planta medica 75, 216-221 [PubMed:19085685]
[show Abstract]
Epigallocatechin gallate (EGCG) is a major green tea polyphenol with pronounced antioxidative activity. The effects of EGCG on lifespan and stress resistance in wild-type N2 and transgenic strains of Caenorhabditis elegans [ HSP-16.2/GFP, MEV-1(KN1), FEM-1(HC17)] were investigated. The expression of HSP-16.2 (induced by the pro-oxidant juglone) and the intracellular levels of H (2)O (2) were inhibited by EGCG treatment. Daily administration of 220 muM EGCG increased the mean lifespan by 10.14 % and 14.27 % in N2 and FEM-1(HC17) strains, respectively, and 55 muM EGCG increased the mean lifespan in MEV-1(KN1) by 16.11 %. The survival rate was also increased under lethal oxidative stress by 65.05 %. These findings suggest that the increased mean lifespan and stress resistance in C. ELEGANS apparently depend, among other factors, on the antioxidant properties of EGCG. | Robertson IM, Li MX, Sykes BD (2009)
Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate.
The Journal of biological chemistry 284, 23012-23023 [PubMed:19542563]
[show Abstract]
Heart muscle contraction is regulated by Ca(2+) binding to the thin filament protein troponin C. In cardiovascular disease, the myofilament response to Ca(2+) is often altered. Compounds that rectify this perturbation are of considerable interest as therapeutics. Plant flavonoids have been found to provide protection against a variety of human illnesses such as cancer, infection, and heart disease. (-)-Epigallocatechin gallate (EGCg), the prevalent flavonoid in green tea, modulates force generation in isolated guinea pig hearts (Hotta, Y., Huang, L., Muto, T., Yajima, M., Miyazeki, K., Ishikawa, N., Fukuzawa, Y., Wakida, Y., Tushima, H., Ando, H., and Nonogaki, T. (2006) Eur. J. Pharmacol. 552, 123-130) and in skinned cardiac muscle fibers (Liou, Y. M., Kuo, S. C., and Hsieh, S. R. (2008) Pflugers Arch. 456, 787-800; and Tadano, N., Yumoto, F., Tanokura, M., Ohtsuki, I., and Morimoto, S. (2005) Biophys. J. 88, 314a). In this study we describe the solution structure of the Ca(2+)-saturated C-terminal domain of troponin C in complex with EGCg. Moreover, we show that EGCg forms a ternary complex with the C-terminal domain of troponin C and the anchoring region of troponin I. The structural evidence indicates that the binding site of EGCg on the C-terminal domain of troponin C is in the hydrophobic pocket in the absence of troponin I, akin to EMD 57033. Based on chemical shift mapping, the binding of EGCg to the C-terminal domain of troponin C in the presence of troponin I may be to a new site formed by the troponin C.troponin I complex. This interaction of EGCg with the C-terminal domain of troponin C.troponin I complex has not been shown with other cardiotonic molecules and illustrates the potential mechanism by which EGCg modulates heart contraction. | Kato K, Long NK, Makita H, Toida M, Yamashita T, Hatakeyama D, Hara A, Mori H, Shibata T (2008)
Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells.
British journal of cancer 99, 647-654 [PubMed:18665171]
[show Abstract]
RECK is a novel tumour suppressor gene that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumour invasion, angiogenesis and metastasis. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the methylation status of the RECK gene and cancer invasion in oral squamous cell carcinoma cell lines. Our results showed that treatment of oral cancer cells with EGCG partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression level of RECK mRNA. Inhibition of MMP-2 and MMP-9 levels was also observed in these cells after treatment with EGCG. Interestingly, EGCG significantly suppressed cancer cell-invasive ability by decreasing the number of invasive foci (P<0.0001) as well as invasion depth (P<0.005) in three-dimensional collagen invasion model. Although further investigation is required to assess the extent of contribution of RECK on MMPs to the suppression of invasive behaviour, these results support the conclusion that EGCG plays a key role in suppressing cell invasion through multiple mechanisms, possibly by demethylation effect on MMP inhibitors such as RECK. | Bose M, Lambert JD, Ju J, Reuhl KR, Shapses SA, Yang CS (2008)
The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice.
The Journal of nutrition 138, 1677-1683 [PubMed:18716169]
[show Abstract]
In this study, we investigated the effects of the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on high-fat-induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. The BW decrease was associated with increased fecal lipids in the high-fat-fed groups (r(2) = 0.521; P < 0.05). EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte chemoattractant protein concentrations in high-fat-fed mice (P < 0.05). EGCG treatment also decreased liver weight, liver triglycerides, and plasma alanine aminotransferase concentrations in high-fat-fed mice (P < 0.05). Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat-induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat-fed control mice (P < 0.05). Our results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat-induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms. | Williamson MP, McCormick TG, Nance CL, Shearer WT (2006)
Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy.
The Journal of allergy and clinical immunology 118, 1369-1374 [PubMed:17157668]
[show Abstract]
BackgroundThe green tea flavonoid, epigallocatechin gallate (EGCG), has been proposed to have an anti-HIV-1 effect by preventing the binding of HIV-1 glycoprotein (gp) 120 to the CD4 molecule on T cells.ObjectiveTo demonstrate that EGCG binds to the CD4 molecule at the gp120 attachment site and inhibits gp120 binding at physiologically relevant levels, thus establishing EGCG as a potential therapeutic treatment for HIV-1 infection.MethodsNuclear magnetic resonance spectroscopy was used to examine the binding of EGCG and control, (-)-catechin, to CD4-IgG2 (PRO 542). Gp120 binding to human CD4+ T cells was analyzed by flow cytometry.ResultsAddition of CD4 to EGCG produced a linear decrease in nuclear magnetic resonance signal intensity from EGCG but not from the control, (-)-catechin. In saturation transfer difference experiments, addition of 5.8 micromol/L CD4 to 310 micromol/L EGCG produced strong saturation at the aromatic rings of EGCG, but identical concentrations of (-)-catechin produced much smaller effects, implying EGCG/CD4 binding strong enough to reduce gp120/CD4 binding substantially. Molecular modeling studies suggested a binding site for EGCG in the D1 domain of CD4, the pocket that binds gp120. Physiologically relevant concentrations of EGCG (0.2 micromol/L) inhibited binding of gp120 to isolated human CD4+ T cells.ConclusionWe have demonstrated clear evidence of high-affinity binding of EGCG to the CD4 molecule with a Kd of approximately 10 nmol/L and inhibition of gp120 binding to human CD4+ T cells.Clinical implicationsEpigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection. | Mizushina Y, Saito A, Tanaka A, Nakajima N, Kuriyama I, Takemura M, Takeuchi T, Sugawara F, Yoshida H (2005)
Structural analysis of catechin derivatives as mammalian DNA polymerase inhibitors.
Biochemical and biophysical research communications 333, 101-109 [PubMed:15950188]
[show Abstract]
The inhibitory activities against DNA polymerases (pols) of catechin derivatives (i.e., flavan-3-ols) such as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, (+)-catechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-epigallocatechin gallate (EGCg) were investigated. Among the eight catechins, some catechins inhibited mammalian pols, with EGCg being the strongest inhibitor of pol alpha and lambda with IC(50) values of 5.1 and 3.8 microM, respectively. EGCg did not influence the activities of plant (cauliflower) pol alpha and beta or prokaryotic pols, and further had no effect on the activities of DNA metabolic enzymes such as calf terminal deoxynucleotidyl transferase, T7 RNA polymerase, and bovine deoxyribonuclease I. EGCg-induced inhibition of pol alpha and lambda was competitive with respect to the DNA template-primer and non-competitive with respect to the dNTP (2'-deoxyribonucleotide 5'-triphosphate) substrate. Tea catechins also suppressed TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation, and the tendency of the pol inhibitory activity was the same as that of anti-inflammation. EGCg at 250 microg was the strongest suppressor of inflammation (65.6% inhibition) among the compounds tested. The relationship between the structure of tea catechins and the inhibition of mammalian pols and inflammation was discussed. | Tachibana H, Koga K, Fujimura Y, Yamada K (2004)
A receptor for green tea polyphenol EGCG.
Nature structural & molecular biology 11, 380-381 [PubMed:15024383]
[show Abstract]
The major polyphenol in green tea, (-)-epigallocatechin-3-gallate (EGCG), has been shown to prevent carcinogenesis. We have identified a receptor that mediates the anticancer activity of EGCG. Expression of the metastasis-associated 67-kDa laminin receptor confers EGCG responsiveness to cancer cells at physiologically relevant concentrations. Experiments using surface plasmon resonance demonstrate binding of EGCG to the 67-kDa laminin receptor with a nanomolar K (d) value. | Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS (2003)
Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.
Cancer research 63, 7563-7570 [PubMed:14633667]
[show Abstract]
Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine-deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity, showing competitive inhibition with a K(i) of 6.89 microM. Studies with structural analogues of EGCG suggest the importance of D and B ring structures in the inhibitory activity. Molecular modeling studies also support this conclusion, and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265), Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h caused a concentration- and time-dependent reversal of hypermethylation of p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined by the appearance of the unmethylation-specific bands in PCR. This was accompanied by the expression of mRNA of these genes as determined by reverse transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was demonstrated by Western blot. Reactivation of some methylation-silenced genes by EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the first time the inhibition of DNA methylation by a commonly consumed dietary constituent and suggest the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis. | Rodríguez-Caso C, Rodríguez-Agudo D, Sánchez-Jiménez F, Medina MA (2003)
Green tea epigallocatechin-3-gallate is an inhibitor of mammalian histidine decarboxylase.
Cellular and molecular life sciences : CMLS 60, 1760-1763 [PubMed:14521154]
[show Abstract]
(-)-epigallocatechin-3-gallate, an antiproliferative and antiangiogenic component of green tea, has been reported to inhibit dopa decarboxylase. In this report,we show that this compound also inhibits histidine decarboxylase, the enzymic activity responsible for histamine biosynthesis. This inhibition was proved by a double approach, activity measurements and UV-Vis spectra of enzyme-bound pyridoxal-5'-phosphate. At 0.1 mM (-)-epi-gallocatechin-3-gallate, histidine decarboxylase activity was inhibited by more than 60% and the typical spectrum of the internal aldimine form shifted to a stable major maximum at 345 nm, suggesting that the compound causes a stable change in the structure of the holoenzyme. Since histamine release is one of the primary events in many inflammatory responses, a new potential application of (-)-epigallocatechin-3-gallate in prevention or treatment of inflammatory processes is suggested by these data. | Brusselmans K, De Schrijver E, Heyns W, Verhoeven G, Swinnen JV (2003)
Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells.
International journal of cancer 106, 856-862 [PubMed:12918062]
[show Abstract]
Chemical inhibitors of fatty acid synthase (FAS) inhibit growth and induce apoptosis in several cancer cell lines in vitro and in tumor xenografts in vivo. Recently the green tea component epigallocatechin-3-gallate (EGCG) was shown to act as a natural inhibitor of FAS in chicken liver extracts. Here we investigated whether EGCG inhibits FAS activity in cultured prostate cancer cells and how this inhibition affects endogenous lipid synthesis, cell proliferation and cell viability. The high levels of FAS activity in LNCaP cells were dose-dependently inhibited by EGCG and this inhibition was paralleled by decreased endogenous lipid synthesis, inhibition of cell growth and induction of apoptosis. In contrast, epicatechin (EC), another closely related green tea polyphenolic compound, which does not inhibit FAS, had no effect on LNCaP cell growth or viability. Treatment of nonmalignant cells with low levels of FAS activity (fibroblasts) with EGCG led to a decrease in growth rate but not to induction of apoptosis. These data indicate that EGCG inhibits FAS activity as efficiently as presently known synthetic inhibitors and selectively causes apoptosis in LNCaP cells but not in nontumoral fibroblasts. These findings establish EGCG as a potent natural inhibitor of FAS in intact cells and strengthen the molecular basis for the use of EGCG as a chemopreventive and therapeutic antineoplastic agent. | Takada M, Ku Y, Habara K, Ajiki T, Suzuki Y, Kuroda Y (2002)
Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human biliary tract carcinoma cells.
World journal of surgery 26, 683-686 [PubMed:12053219]
[show Abstract]
Based on recent evidence that tea consumption contributes to a decreased incidence of human carcinomas, a number of investigators have focused on the mechanisms of cancer prevention by tea extracts, especially green tea polyphenols. Epigallocatechin-3-gallate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. This suggests that EGCG may exert its growth-inhibitory effects through modulation of G1 regulatory proteins such as cdk2 and cdk4. The human biliary tract carcinoma cells (TGBC-2, SK-ChA-1, and NOZC-1) were treated with different doses of EGCG (0, 25, 50, 100, and 200 mM) for 48 hours in cell medium. Cell proliferation was analyzed by WST-1 colorimetric assay. For the cell-invasion analysis, the cells were incubated with 100 mM of EGCG for 2 hours. The cells were then added into a Matrigel-coated Cell Insert. After incubation at 37 degrees C for 24 hours, the cells visible through the Matrigel were counted under the microscope. All human biliary tract cancer cells studied showed a significant suppression of cell growth by EGCG treatment in a dose-dependent manner (27.2%, 16.0%, and 10.1%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at the dose of 200 mM). Epigallocatechin-3-gallate treatment also produced a significant suppression of invasive ability of the carcinoma cells (12.6%, 11.2%, 7.9%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at a dose of 100 mM). These data indicated that EGCG might be a potent biological inhibitor of human biliary tract cancers, reducing their proliferative and invasive activities. |
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