title: Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis.
abstract: Philadelphia-chromosome (Ph1)-positive leukemia cells frequently express death receptors DR4/DR5 for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and show high TRAIL-sensitivity. It has been reported that imatinib damaged cardiomyocytes by triggering endoplasmic reticulum (ER) stress and that ER stress inducers intensified TRAIL-sensitivity of some cancer cells by upregulating DR4/DR5 expression. In fact, ER stress inducers enhanced TRAIL-sensitivity of Ph1-positive leukemia cells by upregulating DR4/DR5 expression. In contrast, imatinib did not induce ER stress responses and unexpectedly downregulated DR4/DR5 expression, indicating that sensitization of Ph1-positive leukemia cells to TRAIL-mediated cellular immunity by imatinib through upregulation of DR4/DR5 expression is unlikely.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inukai
authors.forename: Koshi
authors.initials: K
authors.lastname: Akahane
authors.forename: Kinuko
authors.initials: K
authors.lastname: Hirose
authors.forename: Itaru
authors.initials: I
authors.lastname: Kuroda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Honna
authors.forename: Kumiko
authors.initials: K
authors.lastname: Goi
authors.forename: Keiko
authors.initials: K
authors.lastname: Kagami
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Tauchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Kanji
authors.initials: K
authors.lastname: Sugita
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D015153:Blotting, Western; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014415:Tunicamycin; D019284:Thapsigargin; D000068877:Imatinib Mesylate