title: 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.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ohishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Toume
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Midori A
authors.initials: MA
authors.lastname: Arai
authors.affiliation: Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Sadhu
authors.affiliation: Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
authors.forename: Firoj
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: mish@chiba-u.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Ishibashi
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008968:Molecular Conformation; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D013329:Structure-Activity Relationship; D030014:Tabernaemontana / Q000737:chemistry*; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D051176:beta Catenin; D007050:Ibogaine; C011734:coronardine
keywords: Alkaloid; Apocynaceae; Tabernaemontana divaricata; Wnt signal; β-Catenin