A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis

	A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis
	Wang, W; Liu, HY; Wang, S; Hao, XJ; Li, L
刊名	CELL RESEARCH
	2011
卷号	21 期号:5 页码:730-740
关键词	Wnt small molecule inhibitor tumorigenesis
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.,haoxj@mail.kib.ac.cn ; lli@sibs.ac.cn
英文摘要	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.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	ELEMENT-BINDING PROTEIN ; BETA-CATENIN ; SPIRAEA-JAPONICA ; CHROMOSOMAL INSTABILITY ; COLORECTAL-CANCER ; CYCLIN D1 ; C-JUN ; COMPLEX ; ACTIVATION ; ALKALOIDS
收录类别	SCI
语种	英语
WOS记录号	WOS:000290092500005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/803]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, W,Liu, HY,Wang, S,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, W,Liu, HY,Wang, S,Hao, XJ,&Li, L.(2011).A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis.CELL RESEARCH,21(5),730-740.
MLA	Wang, W,et al."A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer cell tumorigenesis".CELL RESEARCH 21.5(2011):730-740.