期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms18071546
关键词
skin cancer; Nrf2; epigenetics; taxifolin; JB6 P+ cells
资金
- Outstanding Innovative Talents Support Plan of Heilongjiang University of Chinese Medicine [2012RCD05]
- Outstanding Talent Cultivation Fund Project of Heilongjiang University of Chinese Medicine [2012cj02]
- Specialized Research Fund for the Doctoral Program of Higher Education (Ministry of Education) [20132327120002]
- Scientific and Technological Projects of Harbin to Russia [2006AA3BE055]
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells. TAX induced antioxidant response element (ARE)-luciferase activity in HepG2-C8 cells and up-regulated mRNA and protein levels of Nrf2 and its downstream genes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), in JB6 P+ cells. Furthermore, bisulfite genomic sequencing revealed that TAX treatment reduces the methylation level of the first 15 CpGs sites in the Nrf2 promoter. Western blotting showed that TAX inhibits the expression levels of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) proteins. In summary, our results revealed that TAX can induce expression of Nrf2 and its downstream target genes in JB6 P+ cells by CpG demethylation. These finding suggest that TAX may exhibit a skin cancer preventive effect by activating Nrf2 via an epigenetic pathway.
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