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

  • Bioorg Med Chem Lett. 2015 Sep 15;25(18):3937-40. doi: 10.1016/j.bmcl.2015.07.036.
Kensuke Ohishi  1 ,  Kazufumi Toume  1 ,  Midori A Arai  1 ,  Samir K Sadhu  2 ,  Firoj Ahmed  3 ,  Masami Ishibashi  4
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
  • 2. Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh.
  • 3. Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
  • 4. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: [email protected].
PMID: 26231157 DOI: 10.1016/j.bmcl.2015.07.036
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.

Keywords
Alkaloid; Apocynaceae; Tabernaemontana divaricata; Wnt signal; β-Catenin.
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