期刊
LEUKEMIA RESEARCH
卷 38, 期 8, 页码 988-996出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2014.06.005
关键词
Iron chelation; Deferasirox; Deferoxamine; Multiple myeloma; Autophagy; mTOR; p70S6 kinase
资金
- National Cancer Institute [P30CA014089]
- National Institutes of Health [P30 DK048552, S10 RR022508]
We examined the antineoplastic effects of the iron chelators, deferasirox and deferoxamine in multiple myeloma cell lines as well as primary myeloma cells. These iron chelators showed marked antiproliferative activity as well as cytotoxicity toward myeloma cell lines and deferasirox was cytotoxic to bone marrow plasma cells from myeloma patients. We also demonstrate that autophagy induced by iron deprivation is the dominant mechanism that mediates the cytotoxicity of iron chelators in multiple myeloma. Exposure to iron chelators led to repression of mTOR signaling as evidenced by decreased phosphorylation of its target p70S6 kinase. Iron chelation, in particular with deferasirox has the potential to be readily translated to a clinical trial for multiple myeloma. (C) 2014 Elsevier Ltd. All rights reserved.
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