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Title: Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells

Abstract

Highlights: Black-Right-Pointing-Pointer Triptolide inhibited COX-2 expression and the half-life of COX-2 mRNA is decreased. Black-Right-Pointing-Pointer The HuR protein shuttling from nucleus to cytoplasm is inhibited by triptolide. Black-Right-Pointing-Pointer Triptolide inhibited 3 Prime -UTR fluorescence reporter gene activity. Black-Right-Pointing-Pointer COX-2 mRNA binding to HuR is decreased by triptolide in pull-down experiments. -- Abstract: Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-{alpha}-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3 Prime -untranslated region (3 Prime -UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action formore » triptolide which may be important in the treatment of lung cancer.« less

Authors:
; ; ; ; ; ;  [1];  [1]
  1. Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)
Publication Date:
OSTI Identifier:
22207593
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 416; Journal Issue: 1-2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; ANTIBODIES; APOPTOSIS; CYTOPLASM; FLUORESCENCE; GENES; HALF-LIFE; LUNGS; MESSENGER-RNA; NEOPLASMS; PROTEINS; RABBIT TUBES; STABILITY

Citation Formats

Sun, Lixin, Zhang, Shuang, Jiang, Zhenzhou, Huang, Xin, Wang, Tao, Huang, Xiao, Li, Han, and Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.11.004.
Sun, Lixin, Zhang, Shuang, Jiang, Zhenzhou, Huang, Xin, Wang, Tao, Huang, Xiao, Li, Han, & Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells. United States. doi:10.1016/J.BBRC.2011.11.004.
Sun, Lixin, Zhang, Shuang, Jiang, Zhenzhou, Huang, Xin, Wang, Tao, Huang, Xiao, Li, Han, and Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn. Fri . "Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells". United States. doi:10.1016/J.BBRC.2011.11.004.
@article{osti_22207593,
title = {Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells},
author = {Sun, Lixin and Zhang, Shuang and Jiang, Zhenzhou and Huang, Xin and Wang, Tao and Huang, Xiao and Li, Han and Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn},
abstractNote = {Highlights: Black-Right-Pointing-Pointer Triptolide inhibited COX-2 expression and the half-life of COX-2 mRNA is decreased. Black-Right-Pointing-Pointer The HuR protein shuttling from nucleus to cytoplasm is inhibited by triptolide. Black-Right-Pointing-Pointer Triptolide inhibited 3 Prime -UTR fluorescence reporter gene activity. Black-Right-Pointing-Pointer COX-2 mRNA binding to HuR is decreased by triptolide in pull-down experiments. -- Abstract: Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-{alpha}-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3 Prime -untranslated region (3 Prime -UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer.},
doi = {10.1016/J.BBRC.2011.11.004},
journal = {Biochemical and Biophysical Research Communications},
number = 1-2,
volume = 416,
place = {United States},
year = {Fri Dec 09 00:00:00 EST 2011},
month = {Fri Dec 09 00:00:00 EST 2011}
}