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      Retraction: Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE 2 Receptors and Epithelial-to-Mesenchymal Transition

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          Abstract

          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 μM and 1.0 μM 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 μg/ml EGCG) in [1] is similar to Fig 1B (Hs294, 0 μM 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 The Carcinogenesis article [2] was retracted in 2018 [3].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 institutions’ 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.

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          Berberine, an isoquinoline alkaloid, inhibits melanoma cancer cell migration by reducing the expressions of cyclooxygenase-2, prostaglandin E₂ and prostaglandin E₂ receptors.

          Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of berberine, an isoquinoline alkaloid, on human melanoma cancer cell migration and the molecular mechanisms underlying these effects using melanoma cell lines, A375 and Hs294. Using an in vitro cell migration assay, we show that over expression of cyclooxygenase (COX)-2, its metabolite prostaglandin E₂ (PGE₂) and PGE₂ receptors promote the migration of cells. We found that treatment of A375 and Hs294 cells with berberine resulted in concentration-dependent inhibition of migration of these cells, which was associated with a reduction in the levels of COX-2, PGE₂ and PGE₂ receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell migration. Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of COX-2 or PGE₂, enhanced cell migration, whereas berberine inhibited TPA- or PGE₂-promoted cell migration. Berberine reduced the basal levels as well as PGE₂-stimulated expression levels of EP2 and EP4. Treatment of the cells with the EP4 agonist stimulated cell migration and berberine blocked EP4 agonist-induced cell migration activity. Moreover, berberine inhibited the activation of nuclear factor-kappa B (NF-κB), an upstream regulator of COX-2, in A375 cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, inhibited cell migration. Together, these results indicate for the first time that berberine inhibits melanoma cell migration, an essential step in invasion and metastasis, by inhibition of COX-2, PGE₂ and PGE₂ receptors.
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            Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition

            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.
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              RETRACTION

              (2018)
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                Author and article information

                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                31 December 2018
                2018
                31 December 2018
                : 13
                : 12
                : e0210345
                Article
                PONE-D-18-36591
                10.1371/journal.pone.0210345
                6312373
                30596805
                861f7e23-dcc7-4153-a860-99783ac44379
                © 2018 The PLOS ONE Editors

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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                Page count
                Figures: 0, Tables: 0, Pages: 1
                Categories
                Retraction
                Biology and Life Sciences
                Nutrition
                Diet
                Beverages
                Tea
                Medicine and Health Sciences
                Nutrition
                Diet
                Beverages
                Tea
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Membrane Potential
                Receptor Potentials
                Medicine and Health Sciences
                Physiology
                Electrophysiology
                Membrane Potential
                Receptor Potentials
                Research and Analysis Methods
                Biological Cultures
                Cell Cultures
                Cultured Tumor Cells
                Melanoma Cells
                Biology and Life Sciences
                Cell Biology
                Cell Motility
                Cell Migration
                Biology and Life Sciences
                Developmental Biology
                Cell Migration
                Medicine and Health Sciences
                Oncology
                Carcinogenesis
                Medicine and Health Sciences
                Rheumatology

                Uncategorized
                Uncategorized

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