Next Article in Journal
Non-Coding RNAs as Predictive Biomarkers to Current Treatment in Metastatic Colorectal Cancer
Next Article in Special Issue
Reprimo, a Potential p53-Dependent Tumor Suppressor Gene, Is Frequently Hypermethylated in Estrogen Receptor α-Positive Breast Cancer
Previous Article in Journal
Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing
Previous Article in Special Issue
Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(7), 1546; doi:10.3390/ijms18071546

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

1
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Harbin 150040, China
2
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
3
College of Pharmacy, Harbin Medical University, Harbin 150086, China
*
Authors to whom correspondence should be addressed.
Received: 26 May 2017 / Revised: 4 July 2017 / Accepted: 7 July 2017 / Published: 17 July 2017
(This article belongs to the Special Issue Cancer Epigenetics)
View Full-Text   |   Download PDF [2562 KB, uploaded 18 July 2017]   |  

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. View Full-Text
Keywords: skin cancer; Nrf2; epigenetics; taxifolin; JB6 P+ cells skin cancer; Nrf2; epigenetics; taxifolin; JB6 P+ cells
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Kuang, H.; Tang, Z.; Zhang, C.; Wang, Z.; Li, W.; Yang, C.; Wang, Q.; Yang, B.; Kong, A.-N. Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications. Int. J. Mol. Sci. 2017, 18, 1546.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top