title: STI571 (Glivec) induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1, via endoplasmic reticulum stress response.
abstract: STI571 is a specific inhibitor of tyrosine kinases, such as BCR-ABL, platelet-derived growth factor receptor, and c-KIT, and has recently been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). This study demonstrated that STI571 induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1. In these cells, STI571 induced pro-caspase-12 or pro-caspase-7 cleavage and it affected caspase-3 activity and induced the endoplasmic reticulum (ER)-resident chaperone, glucose-regulated protein 78. The STI571-induced cell death was blocked by the protein synthesis inhibitor, cycloheximide. Together, these results suggest that STI571 induces cell death in GIST-T1 cells, at least in part, via the ER stress response.
authors.affiliation: Department of Tumor Surgery, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. nakatanh@med.kochi-u.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakatani
authors.forename: Keijiro
authors.initials: K
authors.lastname: Araki
authors.forename: Toufeng
authors.initials: T
authors.lastname: Jin
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Takeki
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Akimori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Namikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Okamoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Nakano
authors.forename: Takehiro
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Hokimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D018832:Molecular Chaperones / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010879:Piperazines; D011500:Protein Synthesis Inhibitors; D011743:Pyrimidines; D014415:Tunicamycin; D020126:Brefeldin A; D000068877:Imatinib Mesylate; D003513:Cycloheximide; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases