title: Tolfenamic Acid Suppresses Inflammatory Stimuli-Mediated Activation of NF-κB Signaling.
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-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.
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA ; College of Food Engineering and Nutrition Science, Shaanxi Normal University, Xi'an, 741609, P. R. China.
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Shao
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lou
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong, 760749, Republic of Korea.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Kui Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
keywords: Inflammation; NF-kappa B; Tolfenamic acid