A marine bio-functional lipid, fucoxanthinol, attenuates human colorectal cancer stem-like cell tumorigenicity and sphere formation.
A marine bio-functional lipid, fucoxanthinol, attenuates human colorectal cancer stem-like cell tumorigenicity and sphere formation.
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DOI：
10.3164/jcbn.16-112
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发表时间：
2017-07
影响因子：
2.4
通讯作者：
Mutoh M
中科院分区：
文献类型：
--
作者：
Terasaki M;Maeda H;Miyashita K;Tanaka T;Miyamoto S;Mutoh M
岩藻黄质醇 (FuOH) 是从海藻中分离出来的岩藻黄质 (Fx) 的肠道代谢物形式，已知具有多种健康益处，例如预防人类癌症。然而，关于 FuOH 对结直肠癌干细胞 (CCSC) 的影响及其对耐药性、肿瘤发生和癌症复发的贡献的信息很少。在本研究中，我们研究了 FuOH 对两种假定的 CCSC、CD44high/EpCAMhigh 细胞和 HT-29 人结直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显着抑制CD44high/EpCAMhigh细胞的生长，并以剂量依赖性方式解体Csps并诱导细胞内出现许多浓缩的染色质体。 FuOH 对 Csps 变化的 IC50 值为 1.8 µM。 FuOH 下调 Csps 中的 pAkt (Ser473)、PPARβ/δ 和 PPARγ。这些蛋白质在细胞增殖、细胞周期、转移和细胞外粘附中发挥着关键作用。每 3 至 4 天向小鼠施用 FuOH（5 毫克/千克体重）十天后，与未治疗的对照小鼠相比，显着抑制了 Csps 肿瘤的发生。我们的结果表明 FuOH 可用作人类 CCSC 的化学预防剂。
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, CD44high/EpCAMhigh 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 CD44high/EpCAMhigh cells and disintegrated Csps and induced many condensed chromatin bodies in the cells in a dose-dependent manner. The IC50 value of FuOH for these changes in Csps was 1.8 µM. FuOH down-regulated pAkt (Ser473), 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.
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DOI：
10.1016/j.bbagen.2008.01.003
发表时间：
2008-04-01
影响因子：
3
作者：
Das, Swadesh K.;Hashimoto, Takashi;Kanazawa, Kazuki
通讯作者：
Kanazawa, Kazuki
影响因子：
2.2
作者：
Campbell, SJ;Bité, JS;Burridge, TR
通讯作者：
Burridge, TR
DOI：
10.1016/s1357-2725(01)00166-2
发表时间：
2002-07-01
影响因子：
4
作者：
Isacke, CM;Yarwood, H
通讯作者：
Yarwood, H
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
DOI：
10.1016/j.bbrc.2005.05.002
发表时间：
2005-07-01
影响因子：
3.1
作者：
Maeda, H;Hosokawa, M;Miyashita, K
通讯作者：
Miyashita, K