Thalidomide Suppresses the Interleukin 1β-Induced NFκB Signaling Pathway in Colon Cancer Cells

Abstract

Thalidomide has been shown to have both antiinflammatory and antiangiogenic effects in several diseases. However, its cellular target and mechanism of action are poorly understood. We investigated the action mechanism of thalidomide through the NFκB pathway. Thalidomide inhibited interleukin (IL) 1β-induced NFκB transcriptional activation and IL-8 production in Caco-2 colon cancer cells. In addition, thalidomide suppressed NFκB nuclear translocation, IκB degradation, and NFκB-inducing kinase (NIK)-induced NFκB transcriptional activation. These results suggest that the molecular target of the effects of thalidomide may be IκB phosphorylation by IκB kinase (IKK), whose activation follows NIK activation and precedes IκB degradation in the NFκB pathway.