p62 participates in the inhibition of NF-κB signaling and apoptosis induced by sulfasalazine in human glioma U251 cells.
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.
Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
Jing
J
Su
Department of Nursing, First Hospital, Jilin University, Changchun 130021, P.R. China.
Fei
F
Liu
Department of Obstetrics, First Hospital, Jilin University, Changchun 130021, P.R. China.
Meihui
M
Xia
Medical Research Laboratory, Jilin Medical College, Jilin 132013, P.R. China.
Ye
Y
Xu
Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
Xiaoning
X
Li
Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
Jinsong
J
Kang
Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
Yulin
Y
Li
Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
Liankun
L
Sun
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000187:drug effects; D012460:Sulfasalazine / Q000008:administration & dosage
D048868:Adaptor Proteins, Signal Transducing; D016328:NF-kappa B; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D012460:Sulfasalazine