Iron chelator-induced apoptosis via the ER stress pathway in gastric cancer cells

Jung Lim Kim, Dae Hee Lee, Yoo Jin Na, Bo Ram Kim, Yoon A. Jeong, Sun Il Lee, Sanghee Kang, Sung Yup Joung, Suk Young Lee, Sang Cheul Oh, Byung Wook Min

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Many reports have shown the anticancer effects of iron deficient on cancer cells, but the effects of iron-chelators on gastric cancer have not been clearly elucidated. Recently, we reported that iron chelators induced an antiproliferative effect in human malignant lymphoma and myeloid leukemia cells. In the present study, we investigated the antitumor activity of these two iron-chelating agents, deferoxamine (DFO) and deferasirox (DFX), with gastric cancer cell lines, and their apoptosis-inducing effects as the potential mechanism. We found that iron chelators displayed significant antiproliferative activity in human gastric cancer cell lines, which may be attributed to their induction of G1 phase arrest and apoptosis. We also found that iron chelators induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in gastric cancer cells. Taken together, our data suggest that iron chelators induced apoptosis in gastric cancer, involving ROS formation ER stress and JNK activation.

Original languageEnglish
Pages (from-to)9709-9719
Number of pages11
JournalTumor Biology
Volume37
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1

Keywords

  • ER stress
  • Gastric cancer
  • Iron chelator
  • JNK

ASJC Scopus subject areas

  • Cancer Research

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