Journal
BIOCHEMICAL PHARMACOLOGY
Volume 79, Issue 10, Pages 1473-1482Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2010.01.008
Keywords
COX-2; Cyanidin; MEK1; MKK4; Raf-1; UVB
Categories
Funding
- Basic Research Program [20090059628]
- World Class University [R31-2008-00-10056-0]
- Priority Research Centers [2009-0093824]
- National Research Foundation of Korea
- Ministry of Education, Science, and Technology
- Rural Development Administration [20070301-034-042]
- Ministry for Agriculture, Forestry and Fisheries, Republic of Korea. [107055-02]
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Skin cancer is the most frequently diagnosed cancer in the United States. Ultraviolet B (UVB) rays (wavelength 280-320 nm) 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-kappa B 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. Crown Copyright (C) 2010 Published by Elsevier Inc All rights reserved.
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