New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha

Yusnita Rifai; Midori A. Arai; Samir K. Sadhu; Firoj Ahmed; Masami Ishibashi

doi:10.1016/j.bmcl.2010.11.126

New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha

Yusnita Rifai, Midori A. Arai, Samir K. Sadhu, Firoj Ahmed, Masami Ishibashi

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

40 Citations (Scopus)

Abstract

The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.

Original language	English
Pages (from-to)	718-722
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2010.11.126
Publication status	Published - 2011 Jan 15
Externally published	Yes

Keywords

Excoecaria agallocha
GLI1-mediated transcriptional activity
Hedgehog
Inhibitor

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2010.11.126

Cite this

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title = "New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha",

abstract = "The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.",

keywords = "Excoecaria agallocha, GLI1-mediated transcriptional activity, Hedgehog, Inhibitor",

author = "Yusnita Rifai and Arai, {Midori A.} and Sadhu, {Samir K.} and Firoj Ahmed and Masami Ishibashi",

note = "Funding Information: We thank Dr. Fritz Aberger and Gerhard Regl (University of Salzburg) for the kind provision of tetracyclin-regulated HaCaT cells, and Dr. Rune Toftg{\aa}rd (Karolinska Institute) for the 12GLIRE-TKO luciferase plasmid. This work was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) . Copyright: Copyright 2012 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.bmcl.2010.11.126",

language = "English",

volume = "21",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Rifai, Yusnita

AU - Arai, Midori A.

AU - Sadhu, Samir K.

AU - Ahmed, Firoj

AU - Ishibashi, Masami

N1 - Funding Information: We thank Dr. Fritz Aberger and Gerhard Regl (University of Salzburg) for the kind provision of tetracyclin-regulated HaCaT cells, and Dr. Rune Toftgård (Karolinska Institute) for the 12GLIRE-TKO luciferase plasmid. This work was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) . Copyright: Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2011/1/15

Y1 - 2011/1/15

N2 - The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.

AB - The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.

KW - Excoecaria agallocha

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KW - Hedgehog

KW - Inhibitor

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New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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