Dataset Information

Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications.

ABSTRACT: 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.

SUBMITTER: Kuang H

PROVIDER: S-EPMC5536034 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications.

Kuang Haixue H Tang Zhenqiu Z Zhang Chengyue C Wang Zhibin Z Li Wenji W Yang Chunjuan C Wang Qiuhong Q Yang Bingyou B Kong Ah-Ng AN

International journal of molecular sciences 20170717 7

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 <i>Nrf2</i> 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 ...[more]

PMID: 28714938

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Project description:Background and aim Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation. Graphical abstract Image 1 Highlights • Lotus leaf ethanoic extract (LL-EE) had higher quercetin than lotus leaves water extract.• LL-EE reduce the risk of the skin cell carcinogenesis.• LL-EE regulated the cell transformation by NRF2-ARE pathway and regulation of epigenetic DNA methylation.

Dataset Information

Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications.

Publications

Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications.

Similar Datasets

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