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Oncotarget. 2017 Nov 20;8(62):105995-106008. doi: 10.18632/oncotarget.22519. eCollection 2017 Dec 1.

1,8-cineole prevents UVB-induced skin carcinogenesis by targeting the aryl hydrocarbon receptor.

Lee J#1,2, Ha SJ#2,3, Park J2,4, Kim YH2, Lee NH2, Kim YE2, Kim Y2, Song KM2, Jung SK1,2.

Author information

1
Department of Food Biotechnology, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.
2
Division of Functional Food Research, Korea Food Research Institute, Gyeonggi-do 13539, Republic of Korea.
3
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
4
Department of Food Bioscience and Technology, Korea University, Seoul 02841, Republic of Korea.
#
Contributed equally

Abstract

1,8-cineole is a natural monoterpene cyclic ether present in Eucalyptus, and has been reported to exhibit anti-inflammatory and antioxidant effects. However, the preventive effect of 1,8-cineole on skin carcinogenesis and the molecular mechanism of action responsible remains unknown. In the present study, we investigated the effect of 1,8-cineole on UVB-induced skin carcinogenesis. 1,8-cineole inhibited UVB-induced cyclooxygenase-2 (COX-2) protein and mRNA expression and prostaglandin E2 (PGE2) generation in HaCaT cells. 1,8-cineole also inhibited phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and phosphorylation of its upstream kinases, c-Src and epidermal growth factor receptor (EGFR). Quantitative real-time RT-PCR (qRT-PCR) and drug affinity responsive target stability (DARTS) assay results showed that 1,8-cineole suppressed UVB-induced expression of a target gene of the aryl hydrocarbon receptor (AhR), cyp1a1, and directly binds to AhR. Knockdown of AhR suppressed COX-2 expression as well as phosphorylation of ERK1/2 in HaCaT cells. Furthermore, topical treatment of 1,8-cineole on mouse skin delayed tumor incidence and reduced tumor numbers, while inhibiting COX-2 expression in vivo. Taken together, these results suggest that 1,8-cineole is a potent chemopreventive agent that inhibits UVB-induced COX-2 expression by targeting AhR to suppress UVB-induced skin carcinogenesis.

KEYWORDS:

1,8-cineole; aryl hydrocarbon receptor; cyclooxygenase-2; drug affinity responsive target stability; skin cancer

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