Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis

Xiaochun Zhang; Takeshi Inukai; Koshi Akahane; Kinuko Hirose; Itaru Kuroda; Hiroko Honna; Kumiko Goi; Keiko Kagami; Tetsuzo Tauchi; Hideo Yagita; Kanji Sugita

doi:10.1016/j.leukres.2011.03.016

Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis

Leuk Res. 2011 Jul;35(7):940-9. doi: 10.1016/j.leukres.2011.03.016. Epub 2011 Apr 3.

Authors

Xiaochun Zhang¹, Takeshi Inukai, Koshi Akahane, Kinuko Hirose, Itaru Kuroda, Hiroko Honna, Kumiko Goi, Keiko Kagami, Tetsuzo Tauchi, Hideo Yagita, Kanji Sugita

Affiliation

¹ Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

PMID: 21466892
DOI: 10.1016/j.leukres.2011.03.016

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Antiviral Agents / pharmacology
Apoptosis / drug effects*
Benzamides
Blotting, Western
Endoplasmic Reticulum / drug effects*
Endoplasmic Reticulum / metabolism
Endoplasmic Reticulum / pathology
Enzyme Inhibitors / pharmacology
Humans
Imatinib Mesylate
Leukemia / drug therapy
Leukemia / metabolism
Leukemia / pathology*
Philadelphia Chromosome*
Piperazines / pharmacology*
Pyrimidines / pharmacology*
RNA, Messenger / genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
Reverse Transcriptase Polymerase Chain Reaction
TNF-Related Apoptosis-Inducing Ligand / genetics
TNF-Related Apoptosis-Inducing Ligand / metabolism*
Thapsigargin / pharmacology*
Tumor Cells, Cultured
Tunicamycin / pharmacology*

Substances

Antineoplastic Agents
Antiviral Agents
Benzamides
Enzyme Inhibitors
Piperazines
Pyrimidines
RNA, Messenger
Receptors, TNF-Related Apoptosis-Inducing Ligand
TNF-Related Apoptosis-Inducing Ligand
TNFSF10 protein, human
Tunicamycin
Thapsigargin
Imatinib Mesylate