Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells
Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells
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DOI：
10.1016/j.bbrc.2015.02.152
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发表时间：
2015-04-17
影响因子：
3.1
通讯作者：
Kim, Yeong Shik
中科院分区：
文献类型：
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作者：
Lee, Kyung-Mi;Yun, Ji Ho;Kim, Yeong Shik
我们证明了从牛膝根中提取的三萜皂苷，即七叶皂苷IVA甲酯具有抗癌活性。我们在HCT116细胞中深入研究了其分子机制。CME减少了细胞核中β-连环素的含量，并抑制了β-连环素与靶基因启动子中特定DNA序列(TCF结合元件，TBE)的结合。因此，CME似乎减少了细胞周期调节蛋白的表达，如细胞周期蛋白D1，作为β-连环蛋白的代表性靶标，以及CDK2和CDK4。由于细胞周期调节蛋白的减少，CME通过将细胞周期停滞在G0/G1期来抑制细胞增殖。因此，我们建议CME作为一种新的Wnt/β-catenin抑制剂，可以作为一种潜在的结直肠癌治疗药物。(C)2015 Elsevier Inc.保留所有权利。
We demonstrate that chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, has an anticancer activity. We investigate its molecular mechanism in depth in HCT116 cells. CME reduces the amount of beta-catenin in nucleus and inhibits the binding of beta-catenin to specific DNA sequences (TCF binding elements, TBE) in target gene promoters. Thus, CME appears to decrease the expression of cell cycle regulatory proteins such as Cyclin D1, as a representative target for beta-catenin, as well as CDK2 and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase. Therefore, we suggest that CME as a novel Wnt/beta-catenin inhibitor can be a putative agent for the treatment of colorectal cancers. (C) 2015 Elsevier Inc. All rights reserved.