ZFIN ID: ZDB-PUB-140816-11
Ricinine: A pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α
Ohishi, K., Toume, K., Arai, M.A., Sadhu, S.K., Ahmed, F., Mizoguchi, T., Itoh, M., Ishibashi, M.
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:
  • Alkaloids/chemistry
  • Alkaloids/isolation & purification
  • Alkaloids/pharmacology*
  • Animals
  • Casein Kinase Ialpha/metabolism*
  • Cell Survival/drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Plant Stems/chemistry
  • Protein Kinase Inhibitors/chemistry
  • Protein Kinase Inhibitors/isolation & purification
  • Protein Kinase Inhibitors/pharmacology*
  • Pyridones/chemistry
  • Pyridones/isolation & purification
  • Pyridones/pharmacology*
  • Ricinus/chemistry*
  • Signal Transduction/drug effects
  • Structure-Activity Relationship
  • Wnt Proteins/metabolism*
  • Wnt Signaling Pathway/drug effects*
  • Zebrafish/embryology
PubMed: 25124862 Full text @ Bioorg. Med. Chem.
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.