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Dietary phytochemical PEITC restricts tumor development via modulation of epigenetic writers and erasers

Jung Eun Park1, Yang Sun1, Sai Kiang Lim2

  • 1School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.

Scientific Reports
|January 13, 2017
PubMed

Insights

Phenethyl isothiocyanate (PEITC), found in cruciferous vegetables, may prevent cancer by altering epigenetic mechanisms. PEITC impacts histone deacetylases and Polycomb proteins, influencing gene expression and promoting tumor cell death.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Dietary phytochemicals, like phenethyl isothiocyanate (PEITC) from cruciferous vegetables, are linked to reduced cancer risk.
  • The epigenetic mechanisms underlying PEITC's anti-cancer effects are not well understood.

Purpose of the Study:

  • To investigate the molecular basis of phenethyl isothiocyanate (PEITC)-mediated epigenetic tumor restriction.
  • To identify how PEITC affects epigenetic regulators in colon cancer cells.

Main Methods:

  • Colon cancer cells were treated with low-dose PEITC for over one month.
  • Changes in expression profiles of epigenetic writers/erasers and chromatin binding of histone deacetylases (HDACs) and Polycomb-group (PcG) proteins were analyzed.
  • Gene expression, including pro-apoptotic genes and PcG target genes, was assessed.
  • The effect of BMI-1 overexpression on PEITC-induced changes was evaluated.

Main Results:

  • Sustained PEITC exposure led to stable alterations in epigenetic regulators and chromatin binding of HDACs and PcG proteins.
  • PEITC blocked HDAC binding to euchromatin and caused hypomethylation of PcG target genes, which are typically hypermethylated in cancer.
  • PEITC induced pro-apoptotic gene expression in tumor cells.
  • Overexpression of BMI-1 partially reversed PEITC's effects, indicating opposing roles in tumor progression.

Conclusions:

  • Phenethyl isothiocyanate (PEITC) regulates the chromatin binding of key epigenetic writers, erasers, and Polycomb complexes.
  • These epigenetic modifications induced by PEITC contribute to the restriction of tumor development.
  • PEITC and Polycomb proteins appear to have opposing roles in controlling cancer progression.

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