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Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells
- Source :
- Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 68(6)
- Publication Year :
- 2014
-
Abstract
- Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c-jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time-PCR, TRAF2, ASK1 and c-jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c-jun were elevated in MG-132 treated cells. Giving ROS scavenger N-acetyl-L-cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation.
- Subjects :
- X-Box Binding Protein 1
XBP1
Leupeptins
Apoptosis
Regulatory Factor X Transcription Factors
Biology
Cell Line, Tumor
Gene expression
medicine
Humans
Pharmacology
Dose-Response Relationship, Drug
Endoplasmic reticulum
General Medicine
Molecular biology
Cell biology
Up-Regulation
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Cell culture
Unfolded protein response
Proteasome inhibitor
Tumor necrosis factor alpha
Reactive Oxygen Species
Proteasome Inhibitors
medicine.drug
Transcription Factors
Subjects
Details
- ISSN :
- 19506007
- Volume :
- 68
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Biomedicinepharmacotherapy = Biomedecinepharmacotherapie
- Accession number :
- edsair.doi.dedup.....26603a0970390761a04b9e68d47d445d