Edaravone, a known free radical scavenger, enhances X-ray-induced apoptosis at low concentrations

Cancer Lett. 2010 Jul 1;293(1):52-7. doi: 10.1016/j.canlet.2009.12.020. Epub 2010 Jan 25.

Abstract

Edaravone has been reported to have a radioprotective effect at high concentrations. We now report that a lower dose of edaravone enhanced X-ray-induced apoptosis of some cell lines harboring p53 wild-type status, such as MOLT-4, Nalm-6, and HepG2. The knock-down of p53 using siRNA in MOLT-4 cells abolished the radiosensitizing effect of edaravone. Enhanced phosphorylations of p53 at Ser 15 and Ser 20 and up-regulation of PUMA, a p53 target protein, were observed after X-irradiation in the presence of edaravone. We conclude that the low dose of edaravone sensitized cells to X-irradiation by promoting the p53-dependent apoptotic signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Edaravone
  • Free Radical Scavengers / pharmacology*
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Leukemia, T-Cell / drug therapy
  • Leukemia, T-Cell / metabolism
  • Leukemia, T-Cell / pathology
  • Leukemia, T-Cell / radiotherapy
  • Radiation-Sensitizing Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • X-Rays

Substances

  • Free Radical Scavengers
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Edaravone
  • Antipyrine