Green tea catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE2 receptors and epithelial-to-mesenchymal transition.

Green tea catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE2 receptors and epithelial-to-mesenchymal transition.
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DOI:
10.1371/journal.pone.0025224
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Katiyar SK
Katiyar SK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Singh T;Katiyar SK

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Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastatic ability. To develop more effective chemopreventive agents for the prevention of melanoma, we have determined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model. Employing cell invasion assays, we found that the inhibitory effects of green tea catechins on the cell migration were in the order of (-)-epigallocatechin-3-gallate (EGCG)>(-)-epigallocatechin>(-)-epicatechin-3-gallate>(-)-gallocatechin>(-)-epicatechin. Treatment of A375 and Hs294t cells with EGCG resulted in a dose-dependent inhibition of cell migration or invasion of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E2 and PGE2 receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration. EGCG inhibits 12-O-tetradecanoylphorbol-13-acetate-, an inducer of COX-2, and PGE2-induced cell migration of cells. EGCG decreased EP2 agonist (butaprost)- and EP4 agonist (Cay10580)-induced cell migration ability. Moreover, EGCG inhibited the activation of NF-κB/p65, an upstream regulator of COX-2, in A375 melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited cell migration. Inhibition of melanoma cell migration by EGCG was associated with transition of mesenchymal stage to epithelial stage, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin, cytokeratin and desmoglein 2) and a reduction in the levels of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in A375 melanoma cells. Together, these results indicate that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE2 receptors and epithelial-to-mesenchymal transition.
DOI: 10.3390/cancers2042058
发表时间: 2010-12-09
期刊: Cancers
影响因子: 5.2
作者:
Maier HJ;Wirth T;Beug H
通讯作者: Beug H
DOI: 10.1093/carcin/bgp019
发表时间: 2009-03-01
期刊: CARCINOGENESIS
影响因子: 4.7
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发表时间: 2010-02
期刊: Cancer prevention research (Philadelphia, Pa.)
影响因子: --
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Katiyar SK;Vaid M;van Steeg H;Meeran SM
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DOI: 10.1002/mc.20473
发表时间: 2009-03-01
影响因子: 4.6
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DOI: 10.1158/0008-5472.can-06-0218
发表时间: 2006-05-15
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