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 language | English |
|---|---|
| Pages (from-to) | 572-576 |
| Number of pages | 5 |
| Journal | Journal of Natural Products |
| Volume | 75 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 27 2012 |
| Externally published | Yes |
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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 journal › Article
}
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.
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U2 - 10.1021/np200719r
DO - 10.1021/np200719r
M3 - Article
VL - 75
SP - 572
EP - 576
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 4
ER -