TitleAcrylamide up-regulates cyclooxygenase-2 expression through the MEK/ERK signaling pathway in mouse epidermal cells.
Publication TypeJournal Article
Year of Publication2011
AuthorsLim, T-G, Lee, BKyung, Kwon, JYeon, Jung, SKeun, Lee, KWon
JournalFood Chem Toxicol
Volume49
Issue6
Pagination1249-54
Date Published2011 Jun
ISSN1873-6351
KeywordsAcrylamide, Animals, Anticarcinogenic Agents, Butadienes, Carcinogens, Cell Line, Cyclooxygenase 2, Enzyme Inhibitors, Epidermis, Extracellular Signal-Regulated MAP Kinases, Flavonoids, MAP Kinase Kinase Kinases, Mice, NF-kappa B, Nitriles, Signal Transduction, Transcription Factor AP-1, Up-Regulation
Abstract

Acrylamide is formed during cooking processes and is present in many foods. Accumulating evidence suggests that AA is carcinogenic, but the underlying mechanism remains unclear. Here, we investigated the carcinogenesis mechanisms of AA. AA increased the COX-2 expression. Two major transcription factors, AP-1 and NF-κB, were activated by AA treatment. AA induced the ERK phosphorylation, and this was abolished by the treatment of U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. AA-induced expression and promoter activity of COX-2 were suppressed by U0126. U0126 treatment attenuated AA-induced transactivation of AP-1 and NF-κB, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, myricetin, a natural inhibitor of the MEK/ERK signal pathway, reduced AA-induced activation of the COX-2 promoter as well as activation of AP-1 and NF-κB. Collectively, these results suggest that the ability of AA to up-regulate COX-2 expression through the MEK/ERK signaling pathway underlies AA carcinogenicity.

DOI10.1016/j.fct.2011.03.003
Alternate JournalFood Chem. Toxicol.
PubMed ID21385599