TitleCyanidin suppresses ultraviolet B-induced COX-2 expression in epidermal cells by targeting MKK4, MEK1, and Raf-1.
Publication TypeJournal Article
Year of Publication2010
AuthorsKim, J-E, Kwon, JYeon, Seo, SKwon, Son, JEun, Jung, SKeun, Min, SYun, Hwang, MKyung, Heo, Y-S, Lee, KWon, Lee, HJoo
JournalBiochem Pharmacol
Volume79
Issue10
Pagination1473-82
Date Published2010 May 15
ISSN1873-2968
KeywordsAnimals, Anthocyanins, Blotting, Western, Cell Line, Cyclooxygenase 2, Dinoprostone, Epidermis, Immunoprecipitation, MAP Kinase Kinase 1, MAP Kinase Kinase 4, Mice, Proto-Oncogene Proteins c-raf, Signal Transduction, Transcription Factor AP-1, Transcriptional Activation, Ultraviolet Rays
Abstract

Skin cancer is the most frequently diagnosed cancer in the United States. Ultraviolet B (UVB) rays (wavelength: 280-320nm) play a pivotal role in the development of skin cancer by inducing the expression of inflammatory proteins such as cyclooxygenase-2 (COX-2). Cyanidin, the most plentiful of the plant pigments known as anthocyanidins, is a potent chemopreventive agent. In the present study, we examined the molecular mechanisms underlying the chemopreventive activity of cyanidin and identified its molecular targets. Cyanidin inhibited UVB-induced COX-2 expression and prostaglandin E(2) secretion in the epidermal skin cell line JB6 P+ by suppressing the transactivation of nuclear factor-kappaB and activator protein-1 which are well-known transcription factors regulated by mitogen-activated protein kinase. Cyanidin markedly inhibited the phosphorylation of JNK1/2, ERK1/2, and MEK1/2 than the of MKK4 and Raf-1, two upstream kinases of JNK1/2, ERK1/2, and MEK1/2. Cyanidin significantly suppressed the activities of MKK4, MEK1, and Raf-1 through direct binding. Transient transfection of a small interfering RNA specific for MKK4 inhibited the UVB-induced expression of COX-2 in JB6 P+ cells, as did the expression of a dominant-negative ERK2 mutant. We conclude that MKK4, MEK1, and Raf-1 are targets of cyanidin for the suppression of UVB-induced COX-2 expression.

DOI10.1016/j.bcp.2010.01.008
Alternate JournalBiochem. Pharmacol.
PubMed ID20096264