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DNA Microarray Profiling Highlights Nrf2-Mediated Chemoprevention Targeted by Wasabi-Derived Isothiocyanates in HepG2

Phoebe Zapanta Trio1, Atsuyoshi Kawahara2, Shunsuke Tanigawa2

  • 1a United Graduate School of Agricultural Sciences , Kagoshima University , Kagoshima , Japan.

Nutrition and Cancer
|December 3, 2016
PubMed

Insights

Japanese Wasabi compounds, 6-MSITC and 6-MTITC, activate the Nrf2 pathway. 6-MSITC shows potent antioxidant and potential cancer chemopreventive effects by inducing protective genes.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Pharmacology

Background:

  • Wasabi isothiocyanates (ITCs) like 6-MSITC and 6-MTITC are analogs of sulforaphane (SFN).
  • Previous research indicates Wasabi ITCs activate the Nrf2-antioxidant response element pathway and inhibit cyclooxygenase-2.
  • This study provides the first comprehensive analysis of global transcript level changes induced by Wasabi ITCs compared to SFN.

Purpose of the Study:

  • To investigate and compare the global gene expression profiles induced by Wasabi ITCs (6-MSITC, 6-MTITC) and sulforaphane (SFN) in HepG2 cells.
  • To identify key biological pathways modulated by these compounds using gene expression profiling and pathway analysis.
  • To assess the potential chemopreventive role of 6-MSITC through its antioxidant activity and Nrf2 pathway activation.

Main Methods:

  • HepG2 cells were treated with Wasabi ITCs and SFN.
  • Global gene expression profiling was performed using DNA microarray analysis (HG-U133 plus 2.0 oligonucleotide array).
  • Data validation was conducted using RT-PCR and Western blotting; Ingenuity Pathway Analysis (IPA) was employed for pathway identification.

Main Results:

  • 6-MTITC induced the most significant changes in gene expression, altering 114 genes upregulated and 75 downregulated (≥2 fold change).
  • The Nrf2-mediated pathway and glutamate metabolism were identified as common significantly modulated pathways across all treatments.
  • 6-MSITC demonstrated the most potent activation of the Nrf2-mediated pathway.

Conclusions:

  • 6-MSITC and 6-MTITC modulate global gene expression in HepG2 cells, with 6-MTITC showing broader effects and 6-MSITC strongly activating the Nrf2 pathway.
  • The Nrf2-mediated pathway is a key target for Wasabi ITCs, suggesting a role in cellular defense mechanisms.
  • 6-MSITC exhibits potential chemopreventive properties against cancer due to its antioxidant activity and ability to induce cytoprotective genes via Nrf2 activation.

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