Lee Kyung-Mi, Yun Ji Ho, Lee Dong Hwa, Park Young Gyun, Son Kun Ho, Nho Chu Won, Kim Yeong Shik
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, 210-340, Republic of Korea.
Biochem Biophys Res Commun. 2015 Apr 17;459(4):591-6. doi: 10.1016/j.bbrc.2015.02.152. Epub 2015 Mar 5.
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 β-catenin in nucleus and inhibits the binding of β-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 β-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/β-catenin inhibitor can be a putative agent for the treatment of colorectal cancers.
我们证明了日本牛膝根中的三萜皂苷牛膝皂苷IVa甲酯（CME）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-连环蛋白的量，并抑制β-连环蛋白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似乎会降低细胞周期调节蛋白的表达，如作为β-连环蛋白代表性靶标的细胞周期蛋白D1，以及细胞周期蛋白依赖性激酶2（CDK2）和细胞周期蛋白依赖性激酶4（CDK4）。由于细胞周期调节蛋白的减少，CME通过将细胞周期阻滞在G0/G1期来抑制细胞增殖。因此，我们认为CME作为一种新型的Wnt/β-连环蛋白抑制剂可能是一种治疗结直肠癌的潜在药物。
