Iron chelators induce autophagic cell death in multiple myeloma cells.

Academic Article

Abstract

  • 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.
  • Published In

  • Leukemia Research  Journal
  • Keywords

  • Autophagy, Deferasirox, Deferoxamine, Iron chelation, Multiple myeloma, mTOR, p70S6 kinase, Autophagy, Benzoates, Cell Line, Tumor, Cell Proliferation, Deferasirox, Deferoxamine, Drug Evaluation, Preclinical, Humans, Iron Chelating Agents, Multiple Myeloma, Primary Cell Culture, Reactive Oxygen Species, Triazoles
  • Digital Object Identifier (doi)

    Author List

  • Pullarkat V; Meng Z; Donohue C; Yamamoto VN; Tomassetti S; Bhatia R; Krishnan A; Forman SJ; Synold TW
  • Start Page

  • 988
  • End Page

  • 996
  • Volume

  • 38
  • Issue

  • 8