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

作者：Terasaki Masaru^*; Ogawa Yuki; Endo Tetsuya; Maeda Hayato; Hamada Junichi; Osada Kazumi; Miyashita Kazuo; Mutoh Michihiro

来源：Anticancer Research, 2018, 38(4): 2169-2179.

DOI：10.21873/anticanres.12458

• Fucoxanthinol
• colonosphere
• colorectal cancer stem cell
• hypoxia
• metabolite

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 mu M suppressed HIF1 alpha 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 HIF1 alpha expression. Glycine could be a potential predictor for the activity of agents that inhibit sphere formation by hypoxic colonospheres.

• 出版日期2018-4