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STI571 (Glivec) induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1, via endoplasmic reticulum stress response.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2006 May; Vol. 17 (5), pp. 893-7. - Publication Year :
- 2006
-
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.
- Subjects :
- Antineoplastic Agents pharmacology
Benzamides
Blotting, Western
Brefeldin A pharmacology
Caspase 3
Caspase 7
Caspases metabolism
Cell Line, Tumor
Cell Survival drug effects
Cycloheximide pharmacology
Endoplasmic Reticulum metabolism
Endoplasmic Reticulum Chaperone BiP
Flow Cytometry
Gastrointestinal Stromal Tumors metabolism
Gastrointestinal Stromal Tumors pathology
Heat-Shock Proteins metabolism
Humans
Imatinib Mesylate
Molecular Chaperones metabolism
Protein Synthesis Inhibitors pharmacology
Tunicamycin pharmacology
Endoplasmic Reticulum drug effects
Piperazines pharmacology
Pyrimidines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1107-3756
- Volume :
- 17
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 16596277