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

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

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School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Aomori 036-8561, Japan.
Cancer Prevention Laboratories, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Laboratory of Biofunctional Material Chemistry, Division of Marine Bioscience, Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido 041-8611, Japan.
Epidemiology and Preventions Group, Center for Public Health Sciences, National Cancer Center, Tokyo 104-0045, Japan.


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.

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