title: Iron chelator-induced apoptosis via the ER stress pathway in gastric cancer cells.
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.
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Lim
authors.initials: JL
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul, Republic of Korea.|Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Na
authors.affiliation: Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon A
authors.initials: YA
authors.lastname: Jeong
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Korea.
authors.forename: Sun Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Korea.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Korea.
authors.forename: Sung Yup
authors.initials: SY
authors.lastname: Joung
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Suk-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul, Republic of Korea.|Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Cheul
authors.initials: SC
authors.lastname: Oh
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Korea. gsmin@korea.ac.kr.
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Min
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D000077588:Deferasirox; D003676:Deferoxamine / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018613:Microscopy, Confocal; D009367:Neoplasm Staging; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D017262:Siderophores / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014230:Triazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D001565:Benzoates; D014408:Biomarkers, Tumor; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D017262:Siderophores; D014230:Triazoles; D048031:JNK Mitogen-Activated Protein Kinases; D003676:Deferoxamine; D000077588:Deferasirox
keywords: ER stress; Gastric cancer; Iron chelator; JNK