TY - JOUR
T1 - Coronaridine, an iboga type alkaloid from Tabernaemontana divaricata, inhibits the Wnt signaling pathway by decreasing β-catenin mRNA expression
AU - Ohishi, Kensuke
AU - Toume, Kazufumi
AU - Arai, Midori A.
AU - Sadhu, Samir K.
AU - Ahmed, Firoj
AU - Ishibashi, Masami
N1 - Funding Information:
We would like to thank Prof. J. Nathans (John Hopkins University School of Medicine) for the STF/293 cells and Prof. R. T. Moon (University of Washington) for the SuperFOPFlash plasmid. This study was supported by JSPS KAKENHI Grant Numbers 26293022 , 26305001 , 25670045 , 25870128 , and 23404007 and MEXT KAKENHI Grant Number 23102008 , a Grant-in-Aid for Scientific Research on Innovative Areas ‘Chemical Biology of Natural Products’ , the Takeda Science Foundation – Japan, and the Uehara Memorial Foundation – Japan.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/17
Y1 - 2015/8/17
N2 - 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.
AB - 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.
KW - Alkaloid
KW - Apocynaceae
KW - Tabernaemontana divaricata
KW - Wnt signal
KW - β-Catenin
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U2 - 10.1016/j.bmcl.2015.07.036
DO - 10.1016/j.bmcl.2015.07.036
M3 - Article
C2 - 26231157
AN - SCOPUS:84939253048
SN - 0960-894X
VL - 25
SP - 3937
EP - 3940
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 18
M1 - 22925
ER -
