Imatinib-induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress

Jung Lim Kim, Dae Hee Lee, Soyeon Jeong, Bo Ram Kim, Yoo Jin Na, Seong Hye Park, Min Jee Jo, Yoon A. Jeong, Sang Cheul Oh

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Imatinib is a powerful tyrosine kinase inhibitor that specifcally 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 a p opt o sis of ga st r ic ca nc er cel ls by i nvolvi ng end opla sm ic r et ic-ulum (ER) stress-associated activation of c-Jun NH 2 -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.

Original languageEnglish
Pages (from-to)1616-1626
Number of pages11
JournalOncology reports
Issue number3
Publication statusPublished - 2019 Mar


  • C-Jun NH -terminal kinase
  • Endoplasmic reticulum stress
  • Gastric cancer
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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