Abstract 4604: (−)-Epigallocatechin-3-gallate blocked melanoma cancer cell migration by reducing the endogenous expression of COX-2 and its upstream regulator NF-κB
Authors: Santosh K. Katiyar, Tripti Singh
Journal: Cancer Research (2011)

Abstract Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. If recognized and treated early, melanoma is curable, but as the disease progresses its propensity to metastasize make it difficult to treat. Since, melanoma is a highly malignant cancer with a potent capacity to metastasize distantly, an approach that decreases its metastatic ability or the ability of cancer cell migration may facilitate the development of an effective strategy for its treatment and/or prevention. Dietary phytochemicals offer promising new options for the development of more effective strategies for the prevention of cancer cell invasion, migration, or metastasis, and thus can be utilized as complementary and alternative medicine. Therefore, we examined the effect of green tea catechins on human melanoma cancer cell migration and the molecular mechanisms underlying these effects using melanoma cell lines, A375 and Hs294, as in vitro model. Using an in vitro cell migration assay, we found that overexpression of cyclooxygenase-2 (COX-2), its metabolite prostaglandin (PG) E2, and PGE2 receptors promote the migration of cells. Treatment of A375 and Hs294 cells with equimolar concentration of various tea catechins, it was found that (−)-epigallocatechin-3-gallate (EGCG) was most potent in inhibition of cell migration compared to (−)-epicatechin, (−)-gallocatechin, (−)-epigallocatechin and (−)-epicatechin gallate. EGCG 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 EGCG significantly inhibited TPA- or PGE2-promoted cell migration. EGCG 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 EGCG blocked EP4 agonist-induced cell migration activity. Moreover, EGCG inhibited the activation of 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 EGCG inhibit melanoma cell migration, an essential step in invasion and metastasis, by inhibition of COX-2, PGE2 and PGE2 receptors. Further efforts are needed to develop EGCG as a pharmacologically safe agent alone, or in combination with other anti-metastatic drugs, for the treatment of metastatic melanoma in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4604. doi:10.1158/1538-7445.AM2011-4604