Coronaridine, an iboga type alkaloid from Tabernaemontana divaricata, inhibits the Wnt signaling pathway by decreasing ß-catenin mRNA expression.
Bioorg Med Chem Lett
; 25(18): 3937-40, 2015 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-26231157
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/ß-catenin inhibitory activities with IC50 values of 11.5, 6.0, 5.8, and 7.3 µM, respectively. Of these, coronaridine (3) decreased ß-catenin levels in SW480 colon cancer cells, while this decrease in ß-catenin was not suppressed by a co-treatment with 3 and MG132, a proteasome inhibitor. These results suggested that the decrease observed in ß-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 ß-catenin mRNA levels. Thus, coronaridine (3) may inhibit the Wnt signaling pathway by decreasing the mRNA expression of ß-catenin.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Regulação para Baixo
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Tabernaemontana
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Beta Catenina
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Via de Sinalização Wnt
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Ibogaína
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article