Terasaki Masaru, Maeda Hayato, Miyashita Kazuo, Tanaka Takuji, Miyamoto Shingo, Mutoh Michihiro
School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori 036-8561, Japan.
J Clin Biochem Nutr. 2017 Jul;61(1):25-32. doi: 10.3164/jcbn.16-112. Epub 2017 May 16.
Fucoxanthinol (FuOH), an intestinal metabolite form of fucoxanthin (Fx) isolated from marine algae, is known to possess multiple health benefits, such as prevention of human cancer. However, there is little available information about the effects of FuOH on colorectal cancer stem cells (CCSCs) and their contribution to drug resistance, tumorigenesis and cancer recurrence. In the present study, we investigated the anti-proliferative effect of FuOH on two putative CCSCs, CD44/EpCAM cells and colonospheres (Csps) formed by HT-29 human colorectal cancer cells, and the suppressive effects of FuOH on the growth of xenografted tumor. FuOH significantly inhibited the growth of CD44/EpCAM cells and disintegrated Csps and induced many condensed chromatin bodies in the cells in a dose-dependent manner. The IC value of FuOH for these changes in Csps was 1.8 µM. FuOH down-regulated pAkt (Ser), PPARβ/δ and PPARγ in Csps. These proteins play a critical role in cell proliferation, the cell cycle, metastasis and extracellular adhesion. Ten days after the administration of FuOH (5 mg/kg body weight) to the mice every 3 to 4 days significantly suppressed the Csps tumorigenesis when compared to the untreated control mice. Our results suggest that FuOH could be used as a chemopreventive agent against human CCSC.
岩藻黄质醇（FuOH）是从海藻中分离出的岩藻黄质（Fx）的肠道代谢产物，已知具有多种健康益处，如预防人类癌症。然而，关于FuOH对结直肠癌干细胞（CCSCs）的影响及其对耐药性、肿瘤发生和癌症复发的作用，目前可用信息较少。在本研究中，我们研究了FuOH对两种假定的CCSCs（CD44/EpCAM细胞和由HT-29人结肠癌细胞形成的结肠球（Csps））的抗增殖作用，以及FuOH对异种移植肿瘤生长的抑制作用。FuOH以剂量依赖性方式显著抑制CD44/EpCAM细胞的生长，使Csps解体，并在细胞中诱导许多浓缩染色质体。FuOH引起Csps这些变化的IC值为1.8µM。FuOH下调Csps中的pAkt（Ser）、PPARβ/δ和PPARγ。这些蛋白质在细胞增殖、细胞周期、转移和细胞外黏附中起关键作用。与未处理的对照小鼠相比，每3至4天给小鼠施用FuOH（5mg/kg体重）10天后，显著抑制了Csps肿瘤的发生。我们的结果表明，FuOH可作为一种针对人类CCSC的化学预防剂。
