Glycine Is a Predictor for a Suppressive Effect of Fucoxanthinol on Colonosphere Formation Under Hypoxia

Anticancer Res. 2018 Apr;38(4):2169-2179. doi: 10.21873/anticanres.12458.


Background/aim: Fucoxanthinol (FxOH), a metabolite of fucoxanthin, is known to inhibit tumorigenicity of human colorectal cancer stem cells (CCSCs) and their sphere formation. Hypoxic conditions and hypoxia-inducible factors (HIFs) are essential to maintain the stemness of CCSCs. We investigated effects of FxOH on sphere formation, intercellular energy metabolites in colonospheres formed from human colorectal HT-29 cells under hypoxic conditions.

Results: FxOH at 50 μM suppressed HIF1α expression and activation of integrin, mitogen-activated protein kinase (MAPK), Wingless/integrated (WNT) and signal transducer and activator of transcription (STAT) signals. Moreover, expression of epithelial-mesenchymal transition- and apoptosis-related proteins in the colonospheres was lowered by FxOH. The level of glycine was reduced in hypoxic colonospheres under FxOH treatment.

Conclusion: FxOH attenuated the sphere formation of hypoxic colonospheres, in part, by suppressing HIF1α expression. Glycine could be a potential predictor for the activity of agents that inhibit sphere formation by hypoxic colonospheres.

Keywords: Fucoxanthinol; colonosphere; colorectal cancer stem cell; hypoxia; metabolite.

MeSH terms

  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Cell Proliferation / drug effects
  • Drug Monitoring / methods
  • Epithelial-Mesenchymal Transition / drug effects
  • Glycine / analysis
  • Glycine / metabolism
  • Glycine / physiology*
  • HT29 Cells
  • Humans
  • Hypoxia / pathology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology
  • Spheroids, Cellular / drug effects*
  • Spheroids, Cellular / pathology*
  • beta Carotene / analogs & derivatives*
  • beta Carotene / pharmacology


  • Biomarkers, Tumor
  • beta Carotene
  • fucoxanthinol
  • Glycine