Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells.

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.

• Authors: Hai-ying Chen, Xiao-yan Ren, Wei-hua Wang, Ying-xin Zhang, Shuang-feng Chen, Bin Zhang, Le-xin Wang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 68 Issue 6 Pg. 709-13 (Jul 2014) ISSN: 1950-6007 [Electronic] France
• PMID: 25092240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• DNA-Binding Proteins
• Leupeptins
• Proteasome Inhibitors
• Reactive Oxygen Species
• Regulatory Factor X Transcription Factors
• Transcription Factors
• X-Box Binding Protein 1
• XBP1 protein, human
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Apoptosis (drug effects, physiology)
• Cell Line, Tumor
• DNA-Binding Proteins (biosynthesis)
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Neoplastic
• Humans
• Leupeptins (pharmacology)
• Proteasome Inhibitors (pharmacology)
• Reactive Oxygen Species (metabolism)
• Regulatory Factor X Transcription Factors
• Transcription Factors (biosynthesis)
• Up-Regulation (drug effects, physiology)
• X-Box Binding Protein 1