fucoxanthinol and Colorectal-Neoplasms

Fucoxanthin is a marine xanthophyll found in edible brown algae, and a metabolite, fucoxanthinol (FxOH), possesses a potent apoptosis inducing effect in many cancer cells. Chloride intracellular channel 4 (CLIC4) is a member of the CLIC family that plays an important role in cancer development and apoptosis. However, the role of CLIC4 in FxOH-induced apoptosis is not well understood. In this study, we investigated whether CLIC4 affects the apoptotic properties of FxOH in human colorectal cancer (CRC) cells under FxOH treatment. Treating human CRC DLD-1 cells with 5.0 μmol/L FxOH significantly induced apoptosis. FxOH downregulated CLIC4, integrin β1, NHERF2 and pSmad2 (Ser

Topics: Apoptosis; beta Carotene; Cell Proliferation; Chloride Channels; Colorectal Neoplasms; Humans

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.

Topics: Apoptosis; beta Carotene; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glycine; HCT116 Cells; HT29 Cells; Humans; Mitogen-Activated Protein Kinase Kinases; Neoplastic Stem Cells; Spheroids, Cellular; STAT Transcription Factors; Succinic Acid

Fucoxanthin (Fx), one of the major xanthophylls in brown algae, is known to be effective for colorectal cancer (CRC) chemoprevention through inhibiting cell growth, cell cycle and caspase activation. Recently, we observed fucoxanthinol (FuOH), an anti-cancer active metabolite of Fx, treatment of human CRC cells resulted in plenty of living floating cells several hours after exposure, and induced apoptosis. In the present study, we investigated whether FuOH induced anchorage-dependent apoptosis, that is "anoikis", along with integrin signal suppression in human CRC cells. We found that cells exposed to 2.5 μM FuOH clearly showed anti-proliferative and apoptotic effects to DLD-1 cells, human CRC cells. FuOH treatment of DLD-1 cells led to an increase in anoikis-like changes represented by Calcein AM negative/ethidium homodimer-1 positive cell and living floating cells. Moreover, FuOH decreased FAK activation, and altered integrin β1 expression and distribution after 6 h treatment. After 24 h, the cells decreased PPARγ expression and Akt activation and increased integrin β1 expression. Our findings suggested that FuOH can induce anoikis in CRC cells through suppression of integrin signals in human CRC cells.

Topics: Allyl Compounds; Anoikis; Antineoplastic Agents, Phytogenic; beta Carotene; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Curcumin; Dietary Supplements; Focal Adhesion Kinase 1; Gene Expression Regulation, Neoplastic; Humans; Integrin beta1; Isothiocyanates; Lipids; PPAR gamma; Sulfides; Sulfoxides