Glycine and succinic acid are effective indicators of the suppression of epithelial-mesenchymal transition by fucoxanthinol in colorectal cancer stem-like cells

Oncol Rep. 2018 Jul;40(1):414-424. doi: 10.3892/or.2018.6398. Epub 2018 Apr 24.


Fucoxanthinol (FxOH) is a strong anticancer metabolite of fucoxanthin that accumulates in abundance in edible brown algae and promises human health benefits. FxOH has been shown to suppress tumorigenicity and sphere formation in human colorectal cancer stem cell (CCSC)-like spheroids (colonospheres, Csps). In the present study, we aimed to clarify the inhibitory activity of FxOH on epithelial-mesenchymal transition (EMT), which is essential for cancer recurrence and distant metastasis, and to identify intracellular low-molecular-weight metabolites that may be useful for evaluating the cellular effects of FxOH on CCSCs. FxOH significantly suppressed sphere-forming activity, migration and invasion in a dose-dependent manner. In addition, treatment with 50 µmol/l FxOH suppressed N-cadherin and vimentin expression and the activation of integrin signaling linked to EMT suppression by western blot analysis. MAPK signaling and STAT signaling related to cell growth and apoptosis in Csps derived from human CRC HT-29 and HCT116 cells were also altered. According to our metabolite profiling by GC-MS analysis, reduced glycine and succinic acid levels were correlated with EMT suppression and apoptosis induction in Csps. Our data indicate that simple amino acids such as glycine and succinic acid may be good prognostic indicators of physiological changes to CCSCs induced by FxOH treatment.

MeSH terms

  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycine / metabolism
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Succinic Acid / metabolism
  • beta Carotene / analogs & derivatives*
  • beta Carotene / pharmacology


  • STAT Transcription Factors
  • beta Carotene
  • fucoxanthinol
  • Succinic Acid
  • Mitogen-Activated Protein Kinase Kinases
  • Glycine