Isodesacetyluvaricin, an annonaceous acetogenin, specifically inhibits gene expression of cyclooxygenase-2

Tung Ying Wu, I. Hui Yang, Yao Ting Tsai, Jaw Yan Wang, Robert Shiurba, Tusty Jiuan Hsieh, Fang Rong Chang, Wei Chiao Chang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cyclooxygenase-2 (COX-2) is an inducible isoform of the enzyme responsible for the synthesis of several inflammatory mediators. In a search for phytochemicals with anti-inflammatory activity, the COX-2 inhibitory activity of 15 typical Annonaceous acetogenins was examined. Isodesacetyluvaricin (1), from the Formosan tropical fruit tree Annona glabra, exhibited the most potent activity. Reverse transcription PCR was used to test the effect of 1 on epidermal growth factor-stimulated expression of COX-2 in cultures of A431 human epidermoid carcinoma cells. Three hours after exposure to 1 (5 μM), A431 cells had barely detectable levels of COX-2 mRNA. A corresponding but smaller decline in the COX-2 protein appeared on using Western blots. Lipopolysaccharide-stimulated expression of COX-2 in Raw 264.7 mouse leukemic monocyte-macrophages showed a similar decrease. Luciferase assays revealed that cells exposed to 1 had reduced activities of two COX-2 promoter-transcription factors: cAMP response element-binding factor and nuclear factor of activated T-cells. Compound 1 did not affect cell proliferation, as measured by a colorimetric assay, or intracellular store-operated calcium influx, as determined by fluorescence imaging. Thus, 1 may serve as a lead compound for targeting inflammatory diseases as well as angiogenesis and cancer metastasis.

Original languageEnglish
Pages (from-to)572-576
Number of pages5
JournalJournal of Natural Products
Volume75
Issue number4
DOIs
Publication statusPublished - Apr 27 2012
Externally publishedYes

Fingerprint

Acetogenins
Cyclooxygenase 2
Gene expression
Gene Expression
Assays
Annona
NFATC Transcription Factors
Lead compounds
Macrophages
Optical Imaging
Cell proliferation
Phytochemicals
Response Elements
Transcription
Fruits
isodesacetyluvaricin
Luciferases
Cell culture
Epidermal Growth Factor
Reverse Transcription

ASJC Scopus subject areas

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

Cite this

Isodesacetyluvaricin, an annonaceous acetogenin, specifically inhibits gene expression of cyclooxygenase-2. / Wu, Tung Ying; Yang, I. Hui; Tsai, Yao Ting; Wang, Jaw Yan; Shiurba, Robert; Hsieh, Tusty Jiuan; Chang, Fang Rong; Chang, Wei Chiao.

In: Journal of Natural Products, Vol. 75, No. 4, 27.04.2012, p. 572-576.

Research output: Contribution to journalArticle

Wu, Tung Ying ; Yang, I. Hui ; Tsai, Yao Ting ; Wang, Jaw Yan ; Shiurba, Robert ; Hsieh, Tusty Jiuan ; Chang, Fang Rong ; Chang, Wei Chiao. / Isodesacetyluvaricin, an annonaceous acetogenin, specifically inhibits gene expression of cyclooxygenase-2. In: Journal of Natural Products. 2012 ; Vol. 75, No. 4. pp. 572-576.
@article{1ca97597f4ef44c09b6916260971c06d,
title = "Isodesacetyluvaricin, an annonaceous acetogenin, specifically inhibits gene expression of cyclooxygenase-2",
abstract = "Cyclooxygenase-2 (COX-2) is an inducible isoform of the enzyme responsible for the synthesis of several inflammatory mediators. In a search for phytochemicals with anti-inflammatory activity, the COX-2 inhibitory activity of 15 typical Annonaceous acetogenins was examined. Isodesacetyluvaricin (1), from the Formosan tropical fruit tree Annona glabra, exhibited the most potent activity. Reverse transcription PCR was used to test the effect of 1 on epidermal growth factor-stimulated expression of COX-2 in cultures of A431 human epidermoid carcinoma cells. Three hours after exposure to 1 (5 μM), A431 cells had barely detectable levels of COX-2 mRNA. A corresponding but smaller decline in the COX-2 protein appeared on using Western blots. Lipopolysaccharide-stimulated expression of COX-2 in Raw 264.7 mouse leukemic monocyte-macrophages showed a similar decrease. Luciferase assays revealed that cells exposed to 1 had reduced activities of two COX-2 promoter-transcription factors: cAMP response element-binding factor and nuclear factor of activated T-cells. Compound 1 did not affect cell proliferation, as measured by a colorimetric assay, or intracellular store-operated calcium influx, as determined by fluorescence imaging. Thus, 1 may serve as a lead compound for targeting inflammatory diseases as well as angiogenesis and cancer metastasis.",
author = "Wu, {Tung Ying} and Yang, {I. Hui} and Tsai, {Yao Ting} and Wang, {Jaw Yan} and Robert Shiurba and Hsieh, {Tusty Jiuan} and Chang, {Fang Rong} and Chang, {Wei Chiao}",
year = "2012",
month = "4",
day = "27",
doi = "10.1021/np200719r",
language = "English",
volume = "75",
pages = "572--576",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Isodesacetyluvaricin, an annonaceous acetogenin, specifically inhibits gene expression of cyclooxygenase-2

AU - Wu, Tung Ying

AU - Yang, I. Hui

AU - Tsai, Yao Ting

AU - Wang, Jaw Yan

AU - Shiurba, Robert

AU - Hsieh, Tusty Jiuan

AU - Chang, Fang Rong

AU - Chang, Wei Chiao

PY - 2012/4/27

Y1 - 2012/4/27

N2 - Cyclooxygenase-2 (COX-2) is an inducible isoform of the enzyme responsible for the synthesis of several inflammatory mediators. In a search for phytochemicals with anti-inflammatory activity, the COX-2 inhibitory activity of 15 typical Annonaceous acetogenins was examined. Isodesacetyluvaricin (1), from the Formosan tropical fruit tree Annona glabra, exhibited the most potent activity. Reverse transcription PCR was used to test the effect of 1 on epidermal growth factor-stimulated expression of COX-2 in cultures of A431 human epidermoid carcinoma cells. Three hours after exposure to 1 (5 μM), A431 cells had barely detectable levels of COX-2 mRNA. A corresponding but smaller decline in the COX-2 protein appeared on using Western blots. Lipopolysaccharide-stimulated expression of COX-2 in Raw 264.7 mouse leukemic monocyte-macrophages showed a similar decrease. Luciferase assays revealed that cells exposed to 1 had reduced activities of two COX-2 promoter-transcription factors: cAMP response element-binding factor and nuclear factor of activated T-cells. Compound 1 did not affect cell proliferation, as measured by a colorimetric assay, or intracellular store-operated calcium influx, as determined by fluorescence imaging. Thus, 1 may serve as a lead compound for targeting inflammatory diseases as well as angiogenesis and cancer metastasis.

AB - Cyclooxygenase-2 (COX-2) is an inducible isoform of the enzyme responsible for the synthesis of several inflammatory mediators. In a search for phytochemicals with anti-inflammatory activity, the COX-2 inhibitory activity of 15 typical Annonaceous acetogenins was examined. Isodesacetyluvaricin (1), from the Formosan tropical fruit tree Annona glabra, exhibited the most potent activity. Reverse transcription PCR was used to test the effect of 1 on epidermal growth factor-stimulated expression of COX-2 in cultures of A431 human epidermoid carcinoma cells. Three hours after exposure to 1 (5 μM), A431 cells had barely detectable levels of COX-2 mRNA. A corresponding but smaller decline in the COX-2 protein appeared on using Western blots. Lipopolysaccharide-stimulated expression of COX-2 in Raw 264.7 mouse leukemic monocyte-macrophages showed a similar decrease. Luciferase assays revealed that cells exposed to 1 had reduced activities of two COX-2 promoter-transcription factors: cAMP response element-binding factor and nuclear factor of activated T-cells. Compound 1 did not affect cell proliferation, as measured by a colorimetric assay, or intracellular store-operated calcium influx, as determined by fluorescence imaging. Thus, 1 may serve as a lead compound for targeting inflammatory diseases as well as angiogenesis and cancer metastasis.

UR - http://www.scopus.com/inward/record.url?scp=84860344551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860344551&partnerID=8YFLogxK

U2 - 10.1021/np200719r

DO - 10.1021/np200719r

M3 - Article

C2 - 22449077

AN - SCOPUS:84860344551

VL - 75

SP - 572

EP - 576

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 4

ER -