Coronaridine, an iboga type alkaloid from Tabernaemontana divaricata, inhibits the Wnt signaling pathway by decreasing β-catenin mRNA expression

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Abstract Four alkaloids, voacangine (1), isovoacangine (2), coronaridine (3), and coronaridine hydroxyindolenine (4), were isolated from the MeOH extract of Tabernaemontana divaricata aerial parts by activity-guided fractionation for Wnt signal inhibitory activity. Compounds 1-4 exhibited TCF/β-catenin inhibitory activities with IC50 values of 11.5, 6.0, 5.8, and 7.3 μM, respectively. Of these, coronaridine (3) decreased β-catenin levels in SW480 colon cancer cells, while this decrease in β-catenin was not suppressed by a co-treatment with 3 and MG132, a proteasome inhibitor. These results suggested that the decrease observed in β-catenin levels by coronaridine (3) did not depend on a proteasomal degradation process. On the other hand, the treatment of SW480 cells with coronaridine (3) caused a decrease in β-catenin mRNA levels. Thus, coronaridine (3) may inhibit the Wnt signaling pathway by decreasing the mRNA expression of β-catenin.

Original languageEnglish
Article number22925
Pages (from-to)3937-3940
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number18
DOIs
Publication statusPublished - 2015 Aug 17
Externally publishedYes

Keywords

  • Alkaloid
  • Apocynaceae
  • Tabernaemontana divaricata
  • Wnt signal
  • β-Catenin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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