Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity

Takumi Shono; Naoki Ishikawa; Kazufumi Toume; Midori A. Arai; Firoj Ahmed; Samir K. Sadhu; Masami Ishibashi

doi:10.1016/j.bmcl.2015.05.037

Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity

Takumi Shono, Naoki Ishikawa, Kazufumi Toume, Midori A. Arai, Firoj Ahmed, Samir K. Sadhu, Masami Ishibashi

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC₅₀ values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

Original language	English
Pages (from-to)	2735-2738
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2015.05.037
Publication status	Published - 2015 Jun 4
Externally published	Yes

Keywords

Hibiscus ficulneus
Lignans
Wnt signal
β-Catenin

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2015.05.037

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@article{ea99c4856f6e4a5388017c85966b87f6,

title = "Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity",

abstract = "The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.",

keywords = "Hibiscus ficulneus, Lignans, Wnt signal, β-Catenin",

author = "Takumi Shono and Naoki Ishikawa and Kazufumi Toume and Arai, {Midori A.} and Firoj Ahmed and Sadhu, {Samir K.} and Masami Ishibashi",

note = "Funding Information: This study was supported by KAKENHI Grant Number 23102008 from MEXT , Grant Numbers 26305001 and 25870128 from the Japan Society for the Promotion of Science (JSPS), the Uehara Memorial Foundation , Takeda Science Foundation , Hamaguchi Foundation for the advancement of Biochemistry, and the Tokyo Biochemical Research Foundation (TBRF). We are grateful to Prof. J. Nathans (John Hopkins University School of Medicine) for providing us with STF/293 cells and Prof. R.T. Moon (University of Washington) for the SuperFOPflash plasmid. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.All rights reserved.",

year = "2015",

month = jun,

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doi = "10.1016/j.bmcl.2015.05.037",

language = "English",

volume = "25",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity

AU - Shono, Takumi

AU - Ishikawa, Naoki

AU - Toume, Kazufumi

AU - Arai, Midori A.

AU - Ahmed, Firoj

AU - Sadhu, Samir K.

AU - Ishibashi, Masami

N1 - Funding Information: This study was supported by KAKENHI Grant Number 23102008 from MEXT , Grant Numbers 26305001 and 25870128 from the Japan Society for the Promotion of Science (JSPS), the Uehara Memorial Foundation , Takeda Science Foundation , Hamaguchi Foundation for the advancement of Biochemistry, and the Tokyo Biochemical Research Foundation (TBRF). We are grateful to Prof. J. Nathans (John Hopkins University School of Medicine) for providing us with STF/293 cells and Prof. R.T. Moon (University of Washington) for the SuperFOPflash plasmid. Publisher Copyright: © 2015 Elsevier Ltd.All rights reserved.

PY - 2015/6/4

Y1 - 2015/6/4

N2 - The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

AB - The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

KW - Hibiscus ficulneus

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KW - Wnt signal

KW - β-Catenin

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ER -

Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity

Abstract

Keywords

ASJC Scopus subject areas

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