Cyclooxygenase-2 (COX-2), a key mediator of inflammation, and its product, prostaglandin E2 (PGE2), enhance carcinogenesis, particularly in skin. Ultraviolet (UV) B is the most carcinogenic component of solar irradiation, and a crucial role of COX-2 in UVB-mediated skin carcinogenesis has been reported. Here, we investigated the effects of delphinidin, an abundant dietary anthocyanin, on UVB-induced COX-2 upregulation and the underlying molecular mechanism. We found that delphinidin suppressed UVB-induced COX-2 expression in JB6 P+ mouse epidermal cells. COX-2 promoter activity and PGE2 production were also suppressed by delphinidin treatment within non-cytotoxic concentrations. Activator protein-1 and nuclear factor- B, crucial transcription factors involved in COX-2 expression, were activated by UVB and delphinidin abolished this activation. UVB-induced phosphorylation of c-Jun N-terminal kinase, p38 kinase and Akt was inhibited by delphinidin. The activities of mitogenactivated protein kinase kinase (MAPKK) 4 and phosphatidylinositol-3 kinase (PI-3K) were inhibited markedly by delphinidin. A pull-down assay using delphinidin-Sepharose beads revealed that delphinidin binds directly with MAPKK4 or PI-3K in a manner that was competitive with adenosine triphosphate. Moreover, in vivo investigations using mouse skin revealed that the upregulation of COX-2 expression, MAPKK4 activity and PI-3K activity induced by UVB was abolished with delphinidin treatment. Collectively, our results demonstrated that delphinidin targets MAPKK4 and PI-3K directly to suppress COX-2 overexpression, suggesting a potential protective role for delphinidin against UVB-mediated skin carcinogenesis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-426.

©2010 American Association for Cancer Research
2010