p62 participates in the inhibition of NF-κB signaling and apoptosis induced by sulfasalazine in human glioma U251 cells

Oncol Rep. 2015 Jul;34(1):235-43. doi: 10.3892/or.2015.3944. Epub 2015 May 4.


Nuclear factor-κB (NF-κB) is constitutively activated in most malignant gliomas and is involved in cancer progression and drug resistance to chemotherapy. Sulfasalazine (SAS) is a classic inhibitor of NF-κB. Apoptosis and autophagy were induced by SAS accompanied by inhibition of NF-κB signaling in U251 cells. Inhibition of autophagy by 3-MA suppressed the effects of SAS on NF-κB signaling and apoptosis in U251 cells. Multifunctional scaffold protein p62 is well known as an autophagy marker protein and provides crosstalk for important signaling pathways, including NF-κB signaling. SAS-induced decrease in the p62 protein levels may be the result of degradation through autophagy. SAS induced the inhibition of NF-κB signaling and apoptosis at least partly via a p62-dependent effect in U251 cells. Collectively, our data shed light on the link between p62 and the NF-κB signaling pathway, particularly in glioma cells. The results may facilitate the design of more effective targeted therapies for the treatment of tumors in which NF-κB signaling is altered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics*
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Glioma / drug therapy
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • NF-kappa B / genetics*
  • Sequestosome-1 Protein
  • Signal Transduction / drug effects
  • Sulfasalazine / administration & dosage


  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Sulfasalazine