Green tea catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE2 receptors and epithelial-to-mesenchymal transition
Authors: Tripti Singh
Santosh K Katiyar
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: Melanoma; Green tea catechins; Cell migration; COX-2; PGE(2)
Affiliations: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

Abstract:  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)&gt;(-)-epigallocatechin&gt;(-)-epicatechin-3-gallate&gt;(-)-gallocatechin&gt;(-)-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) E(2) and PGE(2) 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 PGE(2)-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, PGE(2) receptors and epithelial-to-mesenchymal transition. 

Retracted: Yes

PubPeer comments:
  Retraction Following publication of this article [1], concerns were raised about similarities involving two figure panels. The second and third panels in Fig 5D (Cay10580, 0.1 u03bcM and 1.0 u03bcM panels) are similar. The University of Alabama at Birmingham confirmed that the original data and records needed to clarify the conditions represented in these two panels are not available. Thus, the quantification data shown in the accompanying bar graph, and the conclusion regarding a concentration-dependent effects of Cay10580 on cell migration, are not supported. Fig 2A (Hs294t, 10 u03bcg ml EGCG) in [1] is similar to Fig 1B (Hs294, 0 u03bcM Berberine) in [2], even though the panel in question is used to represent different experimental conditions in the two articles. The University of Alabama at Birmingham confirmed that original data and records are not available to clarify the identity of the cells and treatment conditions in the reported experiments. The Carcinogenesis article [2] was retracted in 2018 [3]. Following a joint investigation by the Birmingham VA Medical Center and the University of Alabama at Birmingham, the institutions requested retraction of this article, as the conclusions could not be supported by available data. In line with the institutionsu2019 recommendation, PLOS ONE Editors retract this article based upon the unavailability of original data and records and the ambiguous identification of samples and treatments. The authors did not comment on the retraction decision. 31 Dec 2018: The PLOS ONE Editors (2018) Retraction: Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition. PLOS ONE 13(12): e0210345. https: doi.org 10.1371 journal.pone.0210345 View retraction ,