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Abstract
Validation of nutraceutical and pharmaceutical targets is essential for the prediction of physiological and side effects. Epidemiologic evidence and molecular studies suggest that non-melanoma skin cancer is directly associated with excessive exposure to ultraviolet (UV) radiation. The aim of the present study was to evaluate the inhibitory effects of syringic acid on UVB-induced signaling and skin carcinogenesis, and determine the molecular targets. Treatment of human epidermal keratinocytes (HaCaT) cells with syringic acid resulted in the suppression of UVB-induced cyclooxygenase-2, matrix metalloproteinase-1, and prostaglandin E2 expression as well as activator protein-1 activity. Moreover, syringic acid inhibited the UVB-induced phosphorylation of mitogen-activated protein kinases and Akt signaling pathways as well as epidermal growth factor receptor (EGFR). Syringic acid treatment further inhibited intracellular reactive oxygen species and protein-tyrosine phosphatase-κ activity, a regulator of EGFR activation. Syringic acid and the antioxidant N-acetyl-l-cysteine inhibited UVB-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. In vivo, pretreatment of mouse skin with syringic acid significantly suppressed UVB-induced skin tumor incidence in a dose-dependent manner. Overall, these results indicate that syringic acid exerts potent chemopreventive activity in skin carcinogenesis mainly by inhibition of the Nox/PTP-κ/EGFR axis. Syringic acid might serve as an effective chemopreventive and therapeutic agent against UVB-mediated skin cancer.

Author information

Ha SJ1, Lee J2, Park J3, Kim YH4, Lee NH4, Kim YE4, Song KM4, Chang PS5, Jeong CH6, Jung SK7.
1
Division of Functional Food Research, Korea Food Research Institute, Jeolabuk-do 55365, Republic of Korea; Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
2
Division of Functional Food Research, Korea Food Research Institute, Jeolabuk-do 55365, Republic of Korea; Food Biotechnology Program, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.
3
Division of Functional Food Research, Korea Food Research Institute, Jeolabuk-do 55365, Republic of Korea; Department of Food Bioscience and Technology, Korea University, Seoul 02841, Republic of Korea.
4
Division of Functional Food Research, Korea Food Research Institute, Jeolabuk-do 55365, Republic of Korea.
5
Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
6
College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea. Electronic address: chjeong75@kmu.ac.kr.
7
Division of Functional Food Research, Korea Food Research Institute, Jeolabuk-do 55365, Republic of Korea; School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: skjung04@knu.ac.kr.