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Ricinine: A pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α
- Source :
- Bioorganic & Medicinal Chemistry. 22:4597-4601
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
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.
- Subjects :
- Cell Survival
Pyridones
Clinical Biochemistry
Pharmaceutical Science
Biochemistry
Pyrvinium
Structure-Activity Relationship
chemistry.chemical_compound
Alkaloids
Transcription (biology)
GSK-3
Drug Discovery
Animals
Humans
Protein Kinase Inhibitors
Wnt Signaling Pathway
Molecular Biology
Zebrafish
Cells, Cultured
Dose-Response Relationship, Drug
Molecular Structure
Plant Stems
biology
Ricinus
Chemistry
Activator (genetics)
Organic Chemistry
Wnt signaling pathway
Casein Kinase Ialpha
biology.organism_classification
Molecular biology
Wnt Proteins
HEK293 Cells
Molecular Medicine
Casein kinase 1
Signal Transduction
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....dbadccb3e681156a4beb8b646e343a4b