title: 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.affiliation: Oral Maxillofacial Head-Neck Key Laboratory of Medical Biology, and central laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
authors.forename: Hai-ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Oral Maxillofacial Head-Neck Key Laboratory of Medical Biology, and central laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Ren
authors.affiliation: Oral Maxillofacial Head-Neck Key Laboratory of Medical Biology, and central laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Oral Maxillofacial Head-Neck Key Laboratory of Medical Biology, and central laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
authors.forename: Ying-xin
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Oral Maxillofacial Head-Neck Key Laboratory of Medical Biology, and central laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
authors.forename: Shuang-feng
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China. Electronic address: Bin_zhanglc@yahoo.com.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia. Electronic address: lwang@csu.edu.au.
authors.forename: Le-xin
authors.initials: LX
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Apoptosis; ER stress; MG-132; Reactive oxygen species; Tca-8113 cells