Terpenoids and a flavonoid glycoside from Acacia pennata leaves as hedgehog/GLI-mediated transcriptional inhibitors

Yusnita Rifai; Midori A. Arai; Takashi Koyano; Thaworn Kowithayakorn; Masami Ishibashi

doi:10.1021/np1000818

Terpenoids and a flavonoid glycoside from Acacia pennata leaves as hedgehog/GLI-mediated transcriptional inhibitors

Yusnita Rifai, Midori A. Arai, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

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

66 Citations (Scopus)

Abstract

Overexpression of glioma-associated oncogene 1 (GLI1), which has been characterized as a terminal effector and a target gene of the Hedgehog (Hh) signaling pathway, is associated with the development of cancer. A cellular screen was applied utilizing of a GLI-dependent luciferase reporter in human keratinocyte cells (HaCaT) and identified two terpenoids (1 and 2) and a flavonoid glycoside (5) from Acacia pennata as Hh/GLI inhibitors. Compounds 1, 2, and 5 exhibited selective cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells with no toxic effect on normal cells. This result was consistent with a dose-dependent reduction of the protein levels of antiapoptotic BCL-2 and the tumor suppressor patched 1 protein (PTCH). Additionally, treatment of 1 downregulated mRNA expression of Ptch in PANC1, suggesting that the compound has an inhibitory effect on the transcription of Hh/GLI.

Original language	English
Pages (from-to)	995-997
Number of pages	3
Journal	Journal of Natural Products
Volume	73
Issue number	5
DOIs	https://doi.org/10.1021/np1000818
Publication status	Published - 2010 May 28
Externally published	Yes

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

UN SDGs

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

Access to Document

10.1021/np1000818

Cite this

@article{d97776f3118e4a07bd7cdb79001ff89f,

title = "Terpenoids and a flavonoid glycoside from Acacia pennata leaves as hedgehog/GLI-mediated transcriptional inhibitors",

abstract = "Overexpression of glioma-associated oncogene 1 (GLI1), which has been characterized as a terminal effector and a target gene of the Hedgehog (Hh) signaling pathway, is associated with the development of cancer. A cellular screen was applied utilizing of a GLI-dependent luciferase reporter in human keratinocyte cells (HaCaT) and identified two terpenoids (1 and 2) and a flavonoid glycoside (5) from Acacia pennata as Hh/GLI inhibitors. Compounds 1, 2, and 5 exhibited selective cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells with no toxic effect on normal cells. This result was consistent with a dose-dependent reduction of the protein levels of antiapoptotic BCL-2 and the tumor suppressor patched 1 protein (PTCH). Additionally, treatment of 1 downregulated mRNA expression of Ptch in PANC1, suggesting that the compound has an inhibitory effect on the transcription of Hh/GLI.",

author = "Yusnita Rifai and Arai, {Midori A.} and Takashi Koyano and Thaworn Kowithayakorn and Masami Ishibashi",

year = "2010",

month = may,

day = "28",

doi = "10.1021/np1000818",

language = "English",

volume = "73",

pages = "995--997",

journal = "Journal of Natural Products",

issn = "0163-3864",

publisher = "American Chemical Society",

number = "5",

}

TY - JOUR

T1 - Terpenoids and a flavonoid glycoside from Acacia pennata leaves as hedgehog/GLI-mediated transcriptional inhibitors

AU - Rifai, Yusnita

AU - Arai, Midori A.

AU - Koyano, Takashi

AU - Kowithayakorn, Thaworn

AU - Ishibashi, Masami

PY - 2010/5/28

Y1 - 2010/5/28

N2 - Overexpression of glioma-associated oncogene 1 (GLI1), which has been characterized as a terminal effector and a target gene of the Hedgehog (Hh) signaling pathway, is associated with the development of cancer. A cellular screen was applied utilizing of a GLI-dependent luciferase reporter in human keratinocyte cells (HaCaT) and identified two terpenoids (1 and 2) and a flavonoid glycoside (5) from Acacia pennata as Hh/GLI inhibitors. Compounds 1, 2, and 5 exhibited selective cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells with no toxic effect on normal cells. This result was consistent with a dose-dependent reduction of the protein levels of antiapoptotic BCL-2 and the tumor suppressor patched 1 protein (PTCH). Additionally, treatment of 1 downregulated mRNA expression of Ptch in PANC1, suggesting that the compound has an inhibitory effect on the transcription of Hh/GLI.

AB - Overexpression of glioma-associated oncogene 1 (GLI1), which has been characterized as a terminal effector and a target gene of the Hedgehog (Hh) signaling pathway, is associated with the development of cancer. A cellular screen was applied utilizing of a GLI-dependent luciferase reporter in human keratinocyte cells (HaCaT) and identified two terpenoids (1 and 2) and a flavonoid glycoside (5) from Acacia pennata as Hh/GLI inhibitors. Compounds 1, 2, and 5 exhibited selective cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells with no toxic effect on normal cells. This result was consistent with a dose-dependent reduction of the protein levels of antiapoptotic BCL-2 and the tumor suppressor patched 1 protein (PTCH). Additionally, treatment of 1 downregulated mRNA expression of Ptch in PANC1, suggesting that the compound has an inhibitory effect on the transcription of Hh/GLI.

UR - http://www.scopus.com/inward/record.url?scp=77952970051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952970051&partnerID=8YFLogxK

U2 - 10.1021/np1000818

DO - 10.1021/np1000818

M3 - Article

C2 - 20450170

AN - SCOPUS:77952970051

SN - 0163-3864

VL - 73

SP - 995

EP - 997

JO - Journal of Natural Products

JF - Journal of Natural Products

IS - 5

ER -

Terpenoids and a flavonoid glycoside from Acacia pennata leaves as hedgehog/GLI-mediated transcriptional inhibitors

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this