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

Nuclear factor-kappa B (NF-kappa B) 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-kappa B. Apoptosis and autophagy were induced by SAS accompanied by inhibition of NF-kappa B signaling in U251 cells. Inhibition of autophagy by 3-MA suppressed the effects of SAS on NF-kappa B 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-kappa B signaling. SAS-induced decrease in the p62 protein levels may be the result of degradation through autophagy. SAS induced the inhibition of NF-kappa B 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-kappa B 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-kappa B signaling is altered.