Thalidomide suppresses the interleukin 1beta-induced NFkappaB signaling pathway in colon cancer cells

Related Experiment Video

Updated: Aug 8, 2026

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
08:37

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice

Published on: April 21, 2015

Soo Hyun Jin1, Tae Il Kim, Dong Soo Han

  • 1Department of Internal Medicine and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Annals of the New York Academy of Sciences
|December 18, 2002
PubMed

Insights

Thalidomide, an anti-inflammatory drug, inhibits the NF-kappaB pathway by targeting IKK. This action suppresses key signaling events, offering insights into its therapeutic mechanisms for various diseases.

Area of Science:

  • Molecular Biology
  • Immunology
  • Pharmacology

Background:

  • Thalidomide exhibits anti-inflammatory and antiangiogenic properties across diverse diseases.
  • The precise cellular targets and mechanisms underlying thalidomide's effects remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular mechanism of thalidomide action.
  • To explore the role of the Nuclear Factor kappa B (NF-kappaB) pathway in thalidomide's effects.

Main Methods:

  • Utilized Caco-2 colon cancer cells to study thalidomide's impact on NF-kappaB signaling.
  • Assessed thalidomide's inhibition of interleukin (IL)-1beta-induced NF-kappaB transcriptional activation and IL-8 production.
  • Monitored NF-kappaB nuclear translocation, Inhibitor of kappa B (IkappaB) degradation, and NF-kappaB-inducing kinase (NIK)-induced NF-kappaB activation.

Main Results:

  • Thalidomide significantly inhibited IL-1beta-induced NF-kappaB transcriptional activation and IL-8 production in Caco-2 cells.
  • The drug suppressed the nuclear translocation of NF-kappaB and the degradation of IkappaB.
  • Thalidomide also attenuated NIK-induced NF-kappaB transcriptional activation, indicating an upstream effect.

Conclusions:

  • The findings suggest that IkappaB kinase (IKK) phosphorylation of IkappaB is a potential molecular target for thalidomide.
  • This phosphorylation event, occurring after NIK activation and before IkappaB degradation, is crucial in the NF-kappaB pathway.
  • Understanding this mechanism provides critical insights into thalidomide's anti-inflammatory actions and potential therapeutic applications.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice07:34

Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice

Published on: December 16, 2021

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel Disease...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...