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

Yuqing Yang1,2, Irene Yang1,2, Mingnan Cao1,2,3

  • 1Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, 08854, USA.

The AAPS Journal
|April 1, 2018
PubMed

Insights

Fucoxanthin (FX) and astaxanthin (AST), natural compounds, activate the Nrf2 pathway. FX reduces Nrf2 gene methylation, preventing skin cancer by inhibiting cell transformation.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Nuclear factor erythroid-2-related factor-2 (Nrf2) is a key regulator of cellular antioxidant and anti-inflammatory responses.
  • Nrf2 plays a crucial role in defending against diseases linked to oxidative stress and inflammation, including cancer.
  • Epigenetic modifications of the Nrf2 gene are vital for restoring its expression.

Purpose of the Study:

  • To investigate the epigenetic regulation of Nrf2 by astaxanthin (AST) and fucoxanthin (FX) in mouse skin cells.
  • To determine the effects of AST and FX on Nrf2 signaling and TPA-induced skin cell transformation.

Main Methods:

  • Utilized JB6 P+ mouse skin epidermal cells and HepG2-C8 cells.
  • Assessed Nrf2 pathway activation using ARE-luciferase reporter assays.
  • Quantified Nrf2 mRNA and protein levels.
  • Measured colony formation in TPA-induced transformation assays.
  • Analyzed Nrf2 promoter methylation via bisulfite conversion and pyrosequencing.
  • Determined DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activity.

Main Results:

  • Fucoxanthin (FX) induced anti-oxidant response element (ARE)-luciferase activity and upregulated Nrf2 and its downstream genes.
  • Both FX and astaxanthin (AST) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 P+ cell transformation.
  • FX reduced Nrf2 promoter methylation, while both FX and AST decreased DNMT activity without affecting HDAC activity.

Conclusions:

  • Fucoxanthin (FX) activates the Nrf2 signaling pathway through epigenetic demethylation of the Nrf2 gene.
  • FX and AST demonstrate potential in blocking TPA-induced skin cell transformation.
  • These findings suggest health-promoting effects of FX and AST in skin cancer prevention.
Keywords:
Nrf2astaxanthinepigeneticsfucoxanthinskin cancer prevention

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