Format

Send to

Choose Destination
AAPS J. 2018 Feb 20;20(2):32. doi: 10.1208/s12248-018-0197-6.

Fucoxanthin Elicits Epigenetic Modifications, Nrf2 Activation and Blocking Transformation in Mouse Skin JB6 P+ Cells.

Yang Y1,2, Yang I1,2, Cao M1,2,3, Su ZY1,2,4, Wu R1,2, Guo Y1,2, Fang M5, Kong AN6,7.

Author information

1
Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, 08854, USA.
2
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.
3
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, People's Republic of China.
4
Department of Bioscience Technology, Chung Yuan Christian University, 200 Chung Pei Road, Chung Li District, Taoyuan City, 32023, Taiwan, Republic of China.
5
Environmental and Occupational Health Sciences Institute, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, 08854, USA.
6
Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, 08854, USA. kongt@pharmacy.rutgers.edu.
7
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA. kongt@pharmacy.rutgers.edu.

Abstract

Nuclear factor erythroid-2-related factor-2 (Nrf2 or NFE2L2) is a master regulator of the anti-oxidative stress response, which is involved in the defense against many oxidative stress/inflammation-mediated diseases, including anticancer effects elicited by an increasing number of natural products. Our previous studies showed that the epigenetic modification of the Nrf2 gene plays a key role in restoring the expression of Nrf2. In this study, we aimed to investigate the epigenetic regulation of Nrf2 by astaxanthin (AST) and fucoxanthin (FX), carotenoids which are abundant in microalgae and seaweeds, in mouse skin epidermal JB6 P+ cells. FX induced the anti-oxidant response element (ARE)-luciferase and upregulated the mRNA and protein levels of Nrf2 and Nrf2 downstream genes in HepG2-C8 cells overexpressing the ARE-luciferase reporter. Both FX and AST decreased colony formation in 12-Otetradecanoylphorbol-13-acetate (TPA)-induced transformation of JB6 P+ cells. FX decreased the methylation of the Nrf2 promoter region in the JB6 P+ cells by the bisulfite conversion and pyrosequencing. Both FX and AST significantly reduced DNA methyltransferase (DNMT) activity but did not affect histone deacetylase (HDAC) activity in JB6 P+ cells. In summary, our results show that FX activates the Nrf2 signaling pathway, induces the epigenetic demethylation of CpG sites in Nrf2 and blocks the TPA-induced transformation of JB6 P+ cells, indicating the potential health-promoting effects of FX in skin cancer prevention.

KEYWORDS:

Nrf2; astaxanthin; epigenetics; fucoxanthin; skin cancer prevention

PMID:
29603113
PMCID:
PMC6286093
DOI:
10.1208/s12248-018-0197-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center