Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Tolfenamic Acid Suppresses Inflammatory Stimuli-Mediated Activation of NF-κB Signaling

  • Shao, Hong Jun (Department of Nutrition and Food Science, University of Maryland) ;
  • Lou, Zhiyuan (Department of Nutrition and Food Science, University of Maryland) ;
  • Jeong, Jin Boo (Department of Bioresource Sciences, Andong National University) ;
  • Kim, Kui Jin (Department of Nutrition and Food Science, University of Maryland) ;
  • Lee, Jihye (Department of Nutrition and Food Science, University of Maryland) ;
  • Lee, Seong-Ho (Department of Nutrition and Food Science, University of Maryland)
  • Received : 2014.07.24
  • Accepted : 2014.10.07
  • Published : 2015.01.01
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Abstract

Tolfenamic acid (TA) is a traditional non-steroid anti-inflammatory drug (NSAID) and has been broadly used for the treatment of migraines. Nuclear factor kappa B (NF-${\kappa}B$) is a sequence-specific transcription factor and plays a key role in the development and progression of inflammation and cancer. We performed the current study to investigate the underlying mechanisms by which TA suppresses inflammation focusing on NF-${\kappa}B$ pathway in TNF-${\alpha}$ stimulated human normal and cancer cell lines and lipopolysaccharide (LPS)-stimulated mouse macrophages. Different types of human cells (HCT116, HT-29 and HEK293) and mouse macrophages (RAW264.7) were pre-treated with different concentrations of TA and then exposed to inflammatory stimuli such as TNF-${\alpha}$ and LPS. Transcriptional activity of NF-${\kappa}B$, $l{\kappa}B-{\alpha}$-degradation, p65 translocation and mitogen-activated protein kinase (MAPK) activations were measured using luciferase assay and Western blots. Pre-treatment of TA repressed TNF-${\alpha}$- or LPS-stimulated NF-${\kappa}B$ transactivation in a dose-dependent manner. TA treatment reduced degradation of $l{\kappa}B-{\alpha}$ and subsequent translocation of p65 into nucleus. TA significantly down-regulated the phosphorylation of c-Jun N-terminal kinase (JNK). However, TA had no effect on NF-${\kappa}B$ signaling and JNK phosphorylation in HT-29 human colorectal cancer cells. TA possesses anti-inflammatory activities through suppression of JNK/NF-${\kappa}B$ pathway in different types of cells.

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References

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