PUBLICATION
Ricinine: A pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α
- Authors
- Ohishi, K., Toume, K., Arai, M.A., Sadhu, S.K., Ahmed, F., Mizoguchi, T., Itoh, M., Ishibashi, M.
- ID
- ZDB-PUB-140816-11
- Date
- 2014
- Source
- Bioorganic & Medicinal Chemistry 22(17): 4597-601 (Journal)
- Registered Authors
- Itoh, Motoyuki, Mizoguchi, Takamasa
- Keywords
- Alkaloid, Euphorbiaceae, Ricinus communis, Wnt signal, Zebrafish
- MeSH Terms
-
- Dose-Response Relationship, Drug
- Pyridones/chemistry
- Pyridones/isolation & purification
- Pyridones/pharmacology*
- Structure-Activity Relationship
- Zebrafish/embryology
- Molecular Structure
- Protein Kinase Inhibitors/chemistry
- Protein Kinase Inhibitors/isolation & purification
- Protein Kinase Inhibitors/pharmacology*
- Casein Kinase Ialpha/metabolism*
- Wnt Proteins/metabolism*
- Wnt Signaling Pathway/drug effects*
- Animals
- Cells, Cultured
- Plant Stems/chemistry
- Humans
- Alkaloids/chemistry
- Alkaloids/isolation & purification
- Alkaloids/pharmacology*
- HEK293 Cells
- Ricinus/chemistry*
- Signal Transduction/drug effects
- Cell Survival/drug effects
- PubMed
- 25124862 Full text @ Bioorg. Med. Chem.
- CTD
- 25124862
Citation
Ohishi, K., Toume, K., Arai, M.A., Sadhu, S.K., Ahmed, F., Mizoguchi, T., Itoh, M., Ishibashi, M. (2014) Ricinine: A pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α. Bioorganic & Medicinal Chemistry. 22(17):4597-601.
Abstract
Wnt signaling plays important roles in proliferation, differentiation, development of cells, and various diseases. Activity-guided fractionation of the MeOH extract of the Ricinus communis stem led to the isolation of four compounds (1-4). The TCF/β-catenin transcription activities of 1 and 3 were 2.2 and 2.5 fold higher at 20 and 30μM, respectively. Cells treated with ricinine (1) had higher β-catenin and lower of p-β-catenin (ser 33, 37, 45, Thr 41) protein levels, whereas glycogen synthase kinase 3β (GSK3β) and casein kinase 1α (CK1α) protein levels remained unchanged. Cells treated with pyrvinium, an activator of CK1α, had lower β-catenin levels. However, the combined treatment of pyrvinium and 1 led to higher β-catenin levels than those in cells treated with pyrvinium alone, which suggested that 1 inhibited CK1α activity. Furthermore, 1 increased β-catenin protein levels in zebrafish embryos. These results indicated that 1 activated the Wnt signaling pathway by inhibiting CK1α.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping