Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate

Garbisa, Spiridione; Sartor, Luigi; Biggin, Susan; Salvato, Benedetto; Benelli, Roberto; Albini, Adriana

doi:10.1002/1097-0142(20010215)91:4<822::aid-cncr1070>3.0.co;2-g

Cited by 292 publications

(228 citation statements)

References 28 publications

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“…The anticancer effects of polyphenolic compounds from green tea have been attributed, at least in part, to their direct inhibition of matrixins such as the gelatinases [4][5][6]. However, the reported IC 50 values for inhibition of these proteinases of about 20 lM, similar to our findings reported here for two collagenases and ADAM-10, are beyond the concentration attainable following green tea consumption.…”

Section: Discussionsupporting

confidence: 77%

“…The most abundant catechin in green tea is (-)-epigallocatechin gallate (EGCG) with others such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) also present. Anti-inflammatory and anti-mitotic properties have been attributed to these compounds [1-3] and they have also been reported to inhibit certain matrixins such as the gelatinases [4][5][6]. The beneficial effects on a range of clinical conditions including cancer growth and metastasis [7][8][9][10][11], cardiovascular and liver diseases [12] may therefore be due to one or a combination of these properties.…”

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confidence: 99%

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Selective inhibition of ADAMTS‐1, ‐4 and ‐5 by catechin gallate esters

Vankemmelbeke

Jones

Fowles

et al. 2003

European Journal of Biochemistry

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Three mammalian ADAMTS enzymes, ADAMTS-1, -4 and -5, are known to cleave aggrecan at certain glutamyl bonds and are considered to be largely responsible for cartilage aggrecan catabolism observed during the development of arthritis. We have previously reported that certain catechins, polyphenolic compounds found in highest concentration in green tea (Camellia sinensis), are capable of inhibiting cartilage aggrecan breakdown in an in vitro model of cartilage degradation. We have now cloned and expressed recombinant human ADAMTS-1, -4 and -5 and report here that the catechin gallate esters found in green tea potently inhibit the aggrecan-degrading activity of these enzymes, with submicromolar IC 50 values. Moreover, the concentration needed for total inhibition of these members of the ADAMTS group is approximately two orders of magnitude lower than that which is needed to partially inhibit collagenase or ADAM-10 activity. Catechin gallate esters therefore provide selective inhibition of certain members of the ADAMTS group of enzymes and could constitute an important nutritional aid in the prevention of arthritis as well as being part of an effective therapy in the treatment of joint disease and other pathologies involving the action of these enzymes.Keywords: ADAMTS; enzyme inhibition; catechin; gallate; aggrecanase.Green tea, made from the leaves of Camellia sinensis, contains catechins, a group of polyphenolic compounds with antioxidant properties that have been at the centre of investigations into the potential medical benefits of consuming green tea. The most abundant catechin in green tea is (-)-epigallocatechin gallate (EGCG) with others such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) also present. Anti-inflammatory and anti-mitotic properties have been attributed to these compounds [1-3] and they have also been reported to inhibit certain matrixins such as the gelatinases [4][5][6]. The beneficial effects on a range of clinical conditions including cancer growth and metastasis [7][8][9][10][11], cardiovascular and liver diseases [12] may therefore be due to one or a combination of these properties.Aggrecan, a large aggregating proteoglycan, is together with type II collagen the major constituent of articular cartilage. Degradation of cartilage aggrecan has mainly been attributed to the action of glutamyl endopeptidases, termed ÔaggrecanasesÕ. Aggrecan degradation products resulting from aggrecanase action have been found in in vitro cultures of cartilage treated with proinflammatory cytokines as well as in synovial fluid of arthritis patients [13][14][15][16]. To date three mammalian ÔaggrecanasesÕ have been identified: a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1, -4 and -5 [17][18][19]. The ADAMTS enzymes belong to a subgroup of metallopeptidases in Family M12 of Clan MA in the Merops database [20] and are related to the ADAMs and matrixins [21]. So far, at least 18 mammalian ADAMTS enzymes have been identified, most of which remain t...

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Selective inhibition of ADAMTS‐1, ‐4 and ‐5 by catechin gallate esters

Vankemmelbeke

Jones

Fowles

et al. 2003

European Journal of Biochemistry

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“…Similar differential susceptibility has already been reported for other plant compounds, notably for (-)epigallocatechin-3-gallate (18), which inhibits cyclin-dependent kinases (36). Differences in proliferation rates may indeed account for the differential restraint under Hyp-DCHA, and it seems reasonable to expect that in vivo not all types of tumor respond equally to this drug.…”

Section: Discussionsupporting

confidence: 72%

Hyperforin Inhibits Cancer Invasion and Metastasis

Donà

Dell’Aica²,

Pezzato³

et al. 2004

Cancer Research

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126

105

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“…The inhibition of MMP activities observed on zymographic bands after their incubation with the evening primrose polyphenol extract may result from binding of high MW tannins to type IV collagen and, consequently, blocking the access of type IV collagenases to their substrate. The research conducted by Garbisa et al [2001] investigating the inhibition of MMP-2 and -9 activities revealed that EGCG -a low molecular weight (MW) compound -exhibited a higher affi nity towards type IV collagenases than to their substrate (gelatin). On the other hand, high MW tannins exhibited much stronger affi nity to proteins having an open conformation (such as collagen and its denaturation product, gelatin) than to globular proteins [Naczk et al, 2001;Deaville et al, 2007].…”

Section: Discussionmentioning

confidence: 99%

Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa) Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

Szewczyk¹,

Lewandowska²,

Owczarek³

et al. 2014

Pol. J. Food Nutr. Sci.

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Key words: evening primrose, matrix metalloproteinases, cancer Evening primrose (Oenothera paradoxa Hudziok) seeds are a rich source of not only a valuable oil containing an essential fatty acid --linolenic acid (GLA) -but also polyphenols which can be obtained from the biomass remaining after oil pressing. The aim of our studies was to evaluate the infl uence of a polyphenol extract from defatted seeds of evening primrose on human colorectal adenocarcinoma Caco-2 cell proliferation and matrix metalloproteinases (MMPs) synthesis and activity. To assess the effect of evening primrose extract on Caco-2 cell proliferation, crystal violet staining and sulforhodamine B (SRB) assays were used whereas mRNA expression and activity of MMPs were evaluated by RT-PCR and gelatin zymography.The results revealed that the examined polyphenol extract had little infl uence on Caco-2 proliferation, but effectively in a time-and dose-dependent manner inhibited MMP-1, MMP-7, MMP-9 and MMP-14 mRNA synthesis induced by TNF- and TPA. Additionally, zymographic analysis revealed that after 24 h, the polyphenol extract at a concentration of 50 mol/L GAE caused a 10-fold reduction in MMP-9 synthesis. Moreover, this extract might be a potent inhibitor of MMP activity. The results showed that polyphenol extract from evening primrose inhibited PBMC-derived MMP-2 and MMP-9 enzymatic activity in dose-dependent manner. The obtained results indicate that the polyphenol extract from evening primrose seeds could be an inhibitor of proteases involved in tumor progression and metastasis.

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Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate

Cited by 292 publications

References 28 publications

Selective inhibition of ADAMTS‐1, ‐4 and ‐5 by catechin gallate esters

Selective inhibition of ADAMTS‐1, ‐4 and ‐5 by catechin gallate esters

Hyperforin Inhibits Cancer Invasion and Metastasis

Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa) Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

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