Ricinine: A pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α

Kensuke Ohishi, Kazufumi Toume, Midori A. Arai, Samir K. Sadhu, Firoj Ahmed, Takamasa Mizoguchi, Motoyuki Itoh, Masami Ishibashi

研究成果: Article査読

20 被引用数 (Scopus)

抄録

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 30 μM, 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.

本文言語English
ページ(範囲)4597-4601
ページ数5
ジャーナルBioorganic and Medicinal Chemistry
22
17
DOI
出版ステータスPublished - 2014 9 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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