Henryin, an ent-kaurane Diterpenoid, Inhibits Wnt Signaling through Interference with beta-Catenin/TCF4 Interaction in Colorectal Cancer Cells
Li, Xingyao1,3; Pu, Jianxin1; Jiang, Shiyou2,3; Su, Jia1,3; Kong, Lingmei1,3; Mao, Bingyu2; Sun, Handong1; Li, Yan1
2013-07-02
发表期刊PLOS ONE
ISSN1932-6203
卷号8期号:7页码:e68525
摘要Aberrant Wnt/beta-catenin signaling has been strongly associated with the tumorigenesis of human colorectal cancer. Inhibitors of this pathway may then offer therapeutic strategies as well as chemoprevention for this malignant disease. Henryin is an ent-kaurane diterpenoid isolated from Isodon rubescens var. lushanensis, a plant long been used in folk medicine to prevent inflammation and gastrointestinal disease. In the present study, we report that henryin selectively inhibits the proliferation of human colorectal cancer cells with a GI(50) value in the nano-molar range. Microarray analysis and reporter assays showed that henryin worked as a novel antagonist of Wnt signaling pathway. Henryin reduced the expression of Cyclin D1 and C-myc, and induced G1/S phase arrest in HCT116 cells. Concurrently, henryin did not affect the cytosol-nuclear distribution of soluble beta-catenin, but impaired the association of beta-catenin/TCF4 transcriptional complex likely through directly blocking the binding of beta-catenin to TCF4. We also then analyzed the structure-activity relationship among the ent-kaurane type diterpenoids. Our data suggests that henryin, as a novel inhibitor of Wnt signaling, could be a potential candidate for further preclinical evaluation for colon cancer treatment, and as such warrants further exploration.
关键词Beta-catenin Colon-cancer Response Element Activation Expression Pathway Complex Growth Apc Antagonists
资助信息100 Talents Program of the Chinese Academy of Sciences; West Light Foundation of the Chinese Academy of Sciences; Major State Basic Research Development Program of China [2009CB522300]; Natural Science Foundation of China [81173076, 81172939]; Recruited Top Talent of Sciences and Technology of Yunnan Province, China [2009C1120]
学科领域Multidisciplinary Sciences
收录类别SCI
语种英语
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000321341000169
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被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/16741
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, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming, Peoples R China
2.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
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Li, Xingyao,Pu, Jianxin,Jiang, Shiyou,et al. Henryin, an ent-kaurane Diterpenoid, Inhibits Wnt Signaling through Interference with beta-Catenin/TCF4 Interaction in Colorectal Cancer Cells[J]. PLOS ONE,2013,8(7):e68525.
APA Li, Xingyao.,Pu, Jianxin.,Jiang, Shiyou.,Su, Jia.,Kong, Lingmei.,...&Li, Yan.(2013).Henryin, an ent-kaurane Diterpenoid, Inhibits Wnt Signaling through Interference with beta-Catenin/TCF4 Interaction in Colorectal Cancer Cells.PLOS ONE,8(7),e68525.
MLA Li, Xingyao,et al."Henryin, an ent-kaurane Diterpenoid, Inhibits Wnt Signaling through Interference with beta-Catenin/TCF4 Interaction in Colorectal Cancer Cells".PLOS ONE 8.7(2013):e68525.
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