| A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis | |
Wang, Wei1 ; Liu, Haiyang2; Wang, Sheng1; Hao, Xiaojiang2; Li, Lin1
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| 通讯作者 | Li, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China |
| 2011-05-01 | |
| 发表期刊 | CELL RESEARCH
 |
| ISSN | 1001-0602 |
| 卷号 | 21期号:5页码:730-740 |
| 摘要 | The Wnt/beta-catenin signaling pathway is a highly conserved pathway in organism evolution and regulates many biological processes. Aberrant activation of the Wnt/beta-catenin signaling pathway is closely related to tumorigenesis. In order to identify potent small molecules to treat the over-activated Wnt signaling-mediated cancer, such as colon cancer, we established a mammalian cell line-based reporter gene screening system. The screen revealed a diterpenoid derivative, 15-oxospiramilactone (NC043) that inhibits Wnt3a or LiCl-stimulated Top-flash reporter activity in HEK293T cells and growth of colon cancer cells, SW480 and Caco-2. Treatment of SW480 cells with NC043 led to decreases in the mRNA and/or protein expression of Wnt target genes Axin2, Cyclin D1 and Survivin, as well as decreases in the protein levels of Cdc25c and Cdc2. NC043 did not affect the cytosol-nuclear distribution and protein level of soluble beta-catenin, but decreased beta-catenin/TCF4 association in SW480 cells. Moreover, NC043 inhibited anchorage-independent growth and xenograft tumorigenesis of SW480 cells. Collectively these results demonstrate that NC043 is a novel small molecule that inhibits canonical Wnt signaling downstream of beta-catenin stability and may be a potential compound for treating colorectal cancer. |
| 关键词 | Wnt Small Molecule Inhibitor Tumorigenesis |
| 学科领域 | Cell Biology |
| DOI | 10.1038/cr.2011.30 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000290092500005 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/14559 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Wei,Liu, Haiyang,Wang, Sheng,et al. A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis[J]. CELL RESEARCH,2011,21(5):730-740. |
| APA | Wang, Wei,Liu, Haiyang,Wang, Sheng,Hao, Xiaojiang,&Li, Lin.(2011).A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis.CELL RESEARCH,21(5),730-740. |
| MLA | Wang, Wei,et al."A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis".CELL RESEARCH 21.5(2011):730-740. |
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