Imatinib-induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress
- Authors
- Kim, Jung Lim; Lee, Dae-Hee; Jeong, Soyeon; Kim, Bo Ram; Na, Yoo Jin; Park, Seong Hye; Jo, Min Jee; Jeong, Yoon A.; Oh, Sang Cheul
- Issue Date
- Mar-2019
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- imatinib; gastric cancer; endoplasmic reticulum stress; c-Jun NH2-terminal kinase
- Citation
- ONCOLOGY REPORTS, v.41, no.3, pp 1616 - 1626
- Pages
- 11
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- ONCOLOGY REPORTS
- Volume
- 41
- Number
- 3
- Start Page
- 1616
- End Page
- 1626
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2309
- DOI
- 10.3892/or.2018.6945
- ISSN
- 1021-335X
1791-2431
- Abstract
- Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR-ABL, c-KIT, and PDGFR kinases, and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancers. However, the possible anticancer effects of imatinib in gastric cancer have not yet been explored. The present study evaluated the in vitro effects of imatinib on gastric cancer cells and determined the molecular mechanism underlying these effects. We determined that imatinib induced mitochondria-mediated apoptosis of gastric cancer cells by involving endoplasmic reticulum (ER) stress-associated activation of c-Jun NH2-terminal kinase (JNK). We also found that imatinib suppressed cell proliferation in a time- and dose-dependent manner. Cell cycle analysis revealed that imatinib-treated AGS cells were arrested in the G2/M phase of the cell cycle. Moreover, imatinib-treated cells exhibited increased levels of phosphorylated JNK, and of the transcription factor C/EBP homologous protein, an ER stress-associated apoptotic molecule. Results of cell viability assays revealed that treatment with a combination of imatinib and chemotherapy agents irinotecan or 5-Fu synergistically inhibited cell growth, compared with treatment with any of these drugs alone. These data indicated that imatinib exerted cytotoxic effects on gastric cancer cells by inducing apoptosis mediated by reactive oxygen species generation and ER stress-associated JNK activation. Furthermore, we revealed that imatinib induced the apoptosis of gastric cancer cells by inhibiting platelet-derived growth factor receptor signaling. Collectively, our results strongly support the use of imatinib in the treatment of treating gastric cancer.
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- Appears in
Collections - 2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
- 4. Research institute > Institute of Convergence New Drug Development > 1. Journal Articles
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