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

• Published in: Anticancer research Vol. 38; no. 4; pp. 2169 - 2179
• Main Authors: Terasaki, Masaru, Ogawa, Yuki, Endo, Tetsuya, Maeda, Hayato, Hamada, Junichi, Osada, Kazumi, Miyashita, Kazuo, Mutoh, Michihiro
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.04.2018
• Subjects: Apoptosis; Colorectal carcinoma; Energy metabolism; Fucoxanthin; Glycine; Hypoxia; Hypoxia-inducible factor 1a; Kinases; MAP kinase; Mesenchyme; Metabolites; Protein kinase; Proteins; Stem cells; Transcription; Tumorigenicity; Wnt protein; colorectal cancer stem cell; hypoxia; metabolite; colonosphere; Fucoxanthinol
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.12458

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. 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. 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.