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-κB) 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-κB pathway in TNF-α 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-α and LPS. Transcriptional activity of NF-κB, IκB-α-degradation, p65 translocation and
mitogen-activated protein kinase (MAPK) activations were measured using
luciferase assay and Western blots. Pre-treatment of TA repressed TNF-α- or LPS-stimulated NF-κB transactivation in a dose-dependent manner. TA treatment reduced degradation of IκB-α 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-κB signaling and JNK phosphorylation in HT-29 human
colorectal cancer cells. TA possesses anti-inflammatory activities through suppression of JNK/NF-κB pathway in different types of cells.