S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Targeting Nrf2-Keap1 signaling for chemoprevention of skin carcinogenesis with bioactive phytochemicals
- Chun, Kyung-Soo; Kundu, Juthika; Kundu, Joydeb Kumar; Surh, Young-Joon
- Issue Date
- Toxicology Letters, Vol.229 No.1, pp.73-84
- Skin cancer; Phytochemicals; Nrf2; Heme oxygenase-1; Chemoprevention; Antioxidant response elements
- The incidence of skin cancer is increasing worldwide. Over the last several decades, attention has been focused on understanding the molecular basis of skin carcinogenesis and identifying substances for use in chemoprevention of skin cancer. Reactive oxygen species generated by chemical carcinogens or UV irradiation play a key role in skin tumorigenesis. Multiple lines of evidence suggest that cellular antioxidant and/or phase-2 detoxification enzymes, collectively known as cytoprotective proteins, can protect against skin carcinogenesis. A redox sensitive transcription factor, nuclear factor-erythroid related factor-2 (Nrf2), is a master regulator of transcriptional activation of genes encoding cytoprotective proteins. Many chemopreventive phytochemicals are known to activate Nrf2 either by oxidative or covalent modification of its cytosolic repressor Kelch-like ECH-associated protein (Keap1) or by phosphorylation of Nrf2. Upon activation, Nrf2 translocates to the nucleus and binds to the antioxidant response element (ARE) located in the promoter regions of genes encoding cytoprotective proteins. Mice genetically deficient in Nrf2 are highly susceptible to chemically induced skin tumorigenesis and are less responsive to the cytoprotective effects of some chemopreventive phytochemicals. This article highlights the Nrf2-ARE signaling as a prime target for chemoprevention of skin cancer with some phytochemicals. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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