Phenethyl isothiocyanate inhibits colorectal cancer stem cells by suppressing Wnt/β-catenin pathway

Phytother Res. 2018 Dec;32(12):2447-2455. doi: 10.1002/ptr.6183. Epub 2018 Aug 30.

Abstract

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/β-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 μM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/β-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/β-catenin pathway.

Keywords: Wnt/β-catenin pathway; colorectal cancer stem cells; phenethyl isothiocyanate.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Down-Regulation / drug effects
  • Humans
  • Isothiocyanates / pharmacology*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / metabolism

Substances

  • Isothiocyanates
  • beta Catenin
  • phenethyl isothiocyanate