STI571 (Glivec) induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1, via endoplasmic reticulum stress response.
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.
Nakatani
Hajime
H
Department of Tumor Surgery, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. nakatanh@med.kochi-u.ac.jp
Araki
Keijiro
K
Jin
Toufeng
T
Kobayashi
Michiya
M
Sugimoto
Takeki
T
Akimori
Toyokazu
T
Namikawa
Tsutomu
T
Okamoto
Ken
K
Nakano
Takumi
T
Okabayashi
Takehiro
T
Hokimoto
Norihiro
N
Kitagawa
Hiroyuki
H
Taguchi
Takahiro
T
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
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