Reference - Detail
| RRC ID | 72509 |
|---|---|
| Author | Park HY, Toume K, Arai MA, Sadhu SK, Ahmed F, Ishibashi M. |
| Title | Calotropin: a cardenolide from calotropis gigantea that inhibits Wnt signaling by increasing casein kinase 1α in colon cancer cells. |
| Journal | Chembiochem |
| Abstract |
Wnt signaling plays key roles in embryonic development and various human diseases. Activity-guided testing to isolate Wnt signaling inhibitors from the methanol extract of Calotropis gigantea (Asclepiadaceae) exudutes identified six Wnt inhibitory cardenolides (1-6), of which 1, 3, 5, and 6 exhibited potent TCF/β-catenin inhibitory activities (IC50 0.7-3.6 nM). Calotropin (1) inhibited Wnt signaling by decreasing both nuclear and cytosolic β-catenin in a dose-dependent manner, and promoted degradation of β-catenin by increasing the phosphorylation of β-catenin at Ser45 through casein kinase 1α (CK1α). Moreover, 1 significantly increased CK1α protein and mRNA levels. The results suggest that 1 inhibits the Wnt signaling pathway by increasing CK1α protein levels. To the best of our knowledge, calotropin is the first small molecule to increase CK1α levels. |
| Volume | 15(6) |
| Pages | 872-8 |
| Published | 2014-4-14 |
| DOI | 10.1002/cbic.201300786 |
| PMID | 24644251 |
| MeSH | Calotropis / chemistry* Calotropis / metabolism Cardenolides / chemistry* Cardenolides / isolation & purification Cardenolides / pharmacology* Casein Kinase Ialpha / antagonists & inhibitors* Casein Kinase Ialpha / genetics Casein Kinase Ialpha / metabolism Cell Line, Tumor Colonic Neoplasms / metabolism Colonic Neoplasms / pathology Humans Phosphorylation / drug effects RNA, Messenger / metabolism Signal Transduction / drug effects Wnt Proteins / antagonists & inhibitors Wnt Proteins / metabolism beta Catenin / antagonists & inhibitors beta Catenin / metabolism |
| IF | 2.576 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |