School of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.
Research Institute of Health Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.
Nutr Cancer. 2021;73(5):889-898. doi: 10.1080/01635581.2020.1779760. Epub 2020 Jun 17.
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) by 0.6-, 0.7-, 0.7-, and 0.5-fold, respectively, compared with control cells without alteration of Rab35 expression. No colocalizing change was observed in CLIC4-related proteins in either control or FxOH-treated cells. CLIC4 knockdown suppressed cell growth and apoptosis. Interestingly, apoptosis induction by FxOH almost disappeared with CLIC4 knockdown. Our findings suggested that CLIC4 could be involved in FxOH-induced apoptosis in human CRC.
岩藻黄质是一种存在于可食用褐藻中的海洋叶黄素,其代谢产物岩藻黄醇(FxOH)在许多癌细胞中具有很强的诱导细胞凋亡作用。氯离子通道 4(CLIC4)是 CLIC 家族的一员,在癌症的发生和细胞凋亡中发挥着重要作用。然而,CLIC4 在 FxOH 诱导的细胞凋亡中的作用尚不清楚。在这项研究中,我们研究了 CLIC4 是否会影响 FxOH 处理下人结直肠癌细胞(CRC)中 FxOH 诱导的凋亡特性。用 5.0μmol/L FxOH 处理人 CRC DLD-1 细胞可显著诱导细胞凋亡。与未改变 Rab35 表达的对照细胞相比,FxOH 将 CLIC4、整合素 β1、NHERF2 和 pSmad2(Ser)分别下调了 0.6、0.7、0.7 和 0.5 倍,但对氯离子通道 4 相关蛋白的共定位没有影响。CLIC4 敲低抑制细胞生长和凋亡。有趣的是,CLIC4 敲低后,FxOH 诱导的细胞凋亡几乎消失。我们的研究结果表明,CLIC4 可能参与了人 CRC 中 FxOH 诱导的细胞凋亡。