Thalidomide suppresses the interleukin 1beta-induced NFkappaB signaling pathway in colon cancer cells.
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 NFkappaB pathway. Thalidomide inhibited interleukin (IL) 1beta-induced NFkappaB transcriptional activation and IL-8 production in Caco-2 colon cancer cells. In addition, thalidomide suppressed NFkappaB nuclear translocation, IkappaB degradation, and NFkappaB-inducing kinase (NIK)-induced NFkappaB transcriptional activation. These results suggest that the molecular target of the effects of thalidomide may be IkappaB phosphorylation by IkappaB kinase (IKK), whose activation follows NIK activation and precedes IkappaB degradation in the NFkappaB pathway.
Jin
Soo Hyun
SH
Department of Internal Medicine and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Kim
Tae Il
TI
Han
Dong Soo
DS
Shin
Sung Kwan
SK
Kim
Won Ho
WH
D003110:Colonic Neoplasms; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013792:Thalidomide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D013792:Thalidomide