title: Endoplasmic reticulum stress contributes to arsenic trioxide-induced apoptosis in drug-sensitive and -resistant leukemia cells.
abstract: This study characterized the role of endoplasmic reticulum stress (ERS)-related pathways in arsenic trioxide-induced apoptosis in multidrug-resistant leukemia K562/ADM cells. Arsenic trioxide exposure led to much significant induction of apoptosis in K562/ADM cells than the parental K562 cells, and the chaperone proteins glucose-regulated protein 78, CHOP/GADD153, X-box binding protein-1 and caspase-12 were activated to varying degrees. Furthermore, arsenic trioxide stimulation led to inhibition of P-glycoprotein and Bcl-2 expression. This study demonstrates a missing link between arsenic trioxide and ERS-induced apoptosis, and suggests that the greater effects obtained in drug-resistant K562/ADM cells may be mediated by downregulation of P-glycoprotein and Bcl-2 expression.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000 Gansu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Hulai
authors.initials: H
authors.lastname: Wei
authors.forename: Bei
authors.initials: B
authors.lastname: Xie
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001152:Arsenicals; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006131:Growth Inhibitors; D006360:Heat-Shock Proteins; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D053454:Caspase 12; D000077237:Arsenic Trioxide