Biomol Ther.  2015 Jan;23(1):39-44. 10.4062/biomolther.2014.088.

Tolfenamic Acid Suppresses Inflammatory Stimuli-Mediated Activation of NF-kappaB Signaling

• Shao HJ
• Lou Z
• Jeong JB
• Kim KJ
• Lee J
• Lee SH

• KMID: 2380361
• DOI: http://doi.org/10.4062/biomolther.2014.088

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.

Keyword

Tolfenamic acid; NF-kappa B; Inflammation

MeSH Terms

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
JNK Mitogen-Activated Protein Kinases
Luciferases
NF-kappa B
Protein Kinases
Transcription Factors
Tumor Necrosis Factor-alpha