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

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.

• Authors: Kensuke Ohishi, Kazufumi Toume, Midori A Arai, Samir K Sadhu, Firoj Ahmed, Masami Ishibashi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 18 Pg. 3937-40 (Sep 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26231157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• RNA, Messenger
• beta Catenin
• Ibogaine
• coronardine

Topics

• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Humans
• Ibogaine (analogs & derivatives, chemistry, isolation & purification, pharmacology)
• Molecular Conformation
• RNA, Messenger (biosynthesis, genetics)
• Structure-Activity Relationship
• Tabernaemontana (chemistry)
• Wnt Signaling Pathway (drug effects, genetics)
• beta Catenin (genetics)