苯乙基异硫氰酸酯在体外和异种移植模型中抑制癌症干细胞特性。
Phenethyl isothiocyanate suppresses cancer stem cell properties in vitro and in a xenograft model.
机构信息
Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Department of Life Science, Sogang University, Seoul 04107, Korea.
Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Daejeon 34113, Korea.
出版信息
Phytomedicine. 2017 Jul 1;30:42-49. doi: 10.1016/j.phymed.2017.01.015. Epub 2017 Feb 3.
BACKGROUND
Cancer stem cells (CSCs) are a subset of cells within the bulk of a tumor that have the ability to self-renew and differentiate, and are thus associated with cancer invasion, metastasis, and recurrence. Phenethyl isothiocyanate (PEITC) is a natural compound found in cruciferous vegetables such as broccoli and is used as a cancer chemopreventive agent; however, its effects on CSCs are little known.
PURPOSE
To evaluate the effect of PEITC on CSCs in this study by examining CSC properties.
METHODS
NCCIT human embryonic carcinoma cells were treated with PEITC, and the expression of pluripotency factors Oct4, Sox-2, and Nanog were evaluated by luciferase assay and western blot. Effect of PEITC on self-renewal capacity and clonogenicity were assessed with the sphere formation, soft agar assay, and clonogenic assay in an epithelial cell adhesion molecule (EpCAM)-expressing CSC model derived from HCT116 colon cancer cells using a cell sorting system. The effect of PEITC was also investigated in a mouse xenograft model obtained by injecting nude mice with EpCAM-expressing cells.
RESULTS
We found that PEITC treatment suppressed expression of the all three pluripotency factors in the NCCIT cells, in which pluripotency factors are highly expressed. Moreover, PEITC suppressed the self-renewal capacity and clonogenicity in the EpCAM-expressing CSC model. EpCAM was used as a specific CSC marker in this study. Importantly, PEITC markedly suppressed both tumor growth and expression of three pluripotency factors in a mouse xenograft model.
CONCLUSION
These results demonstrate that PEITC might be able to slow down or prevent cancer recurrence by suppressing CSC stemness.
背景
癌症干细胞（CSCs）是肿瘤实体中的一小部分细胞，具有自我更新和分化的能力，因此与癌症侵袭、转移和复发有关。苯乙基异硫氰酸酯（PEITC）是一种存在于西兰花等十字花科蔬菜中的天然化合物，可用作癌症化学预防剂；然而，其对 CSCs 的影响知之甚少。
目的
通过研究 CSC 特性，评估 PEITC 对 CSCs 的影响。
方法
用 PEITC 处理 NCCIT 人胚胎癌细胞，通过荧光素酶检测和 Western blot 评估多能性因子 Oct4、Sox-2 和 Nanog 的表达。使用细胞分选系统，从 HCT116 结肠癌细胞中衍生的表达上皮细胞黏附分子（EpCAM）的 CSC 模型中，通过球体形成、软琼脂测定和集落形成测定评估 PEITC 对自我更新能力和克隆形成能力的影响。还在注射表达 EpCAM 的细胞的裸鼠中进行了 PEITC 的体内实验。
结果
我们发现，PEITC 处理抑制了 NCCIT 细胞中三种多能性因子的表达，而这些因子在 NCCIT 细胞中高度表达。此外，PEITC 抑制了 EpCAM 表达的 CSC 模型中的自我更新能力和克隆形成能力。在本研究中，EpCAM 被用作特异性 CSC 标志物。重要的是，PEITC 显著抑制了裸鼠异种移植模型中的肿瘤生长和三种多能性因子的表达。
结论
这些结果表明，PEITC 通过抑制 CSC 干性，可能能够减缓或预防癌症复发。
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