Tolfenamic Acid Suppresses Inflammatory Stimuli-Mediated Activation of NF-kappaB Signaling.
10.4062/biomolther.2014.088
- Author:
Hong Jun SHAO
1
;
Zhiyuan LOU
;
Jin Boo JEONG
;
Kui Jin KIM
;
Jihye LEE
;
Seong Ho LEE
Author Information
1. Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA. slee2000@umd.edu
- Publication Type:Original Article
- Keywords:
Tolfenamic acid;
NF-kappa B;
Inflammation
- MeSH:
Animals;
Blotting, Western;
Cell Line;
Colorectal Neoplasms;
Humans;
Inflammation;
JNK Mitogen-Activated Protein Kinases;
Luciferases;
Macrophages;
Mice;
Migraine Disorders;
NF-kappa B*;
Phosphorylation;
Protein Kinases;
Transcription Factors;
Transcriptional Activation;
Tumor Necrosis Factor-alpha
- From:Biomolecules & Therapeutics
2015;23(1):39-44
- CountryRepublic of Korea
- Language:English
-
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-kappaB) 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-kappaB 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-kappaB, IkappaB-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-kappaB transactivation in a dose-dependent manner. TA treatment reduced degradation of IkappaB-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-kappaB signaling and JNK phosphorylation in HT-29 human colorectal cancer cells. TA possesses anti-inflammatory activities through suppression of JNK/NF-kappaB pathway in different types of cells.
