Free radical scavenger edaravone suppresses x-ray-induced apoptosis through p53 inhibition in MOLT-4 cells

J Radiat Res. 2007 Nov;48(6):495-503. doi: 10.1269/jrr.07061. Epub 2007 Oct 24.

Abstract

Edaravone, a clinical drug used widely for the treatment of acute cerebral infarction, is reported to scavenge free radicals. In the present study, we investigated the radioprotective effect of edaravone on X-ray-induced apoptosis in MOLT-4 cells. Apoptosis was determined by the dye exclusion test, Annexin V binding assay, cleavage of caspase, and DNA fragmentation. We found that edaravone significantly suppressed the X-ray-induced apoptosis. The amount of intracellular ROS production was determined by the chloromethyl-2',7'-dichlorodihydro-fluorescein diacetate system. We found that the intracellular ROS production by X-irradiation was completely suppressed by the addition of edaravone. The accumulation and phosphorylation of p53 and the expression of p21(WAF1), a target protein of p53, which were induced by X-irradiation, were also suppressed by adding edaravone. We conclude that the free radical scavenger edaravone suppresses X-ray-induced apoptosis in MOLT-4 cells by inhibiting p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipyrine / administration & dosage
  • Antipyrine / analogs & derivatives*
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Edaravone
  • Free Radical Scavengers / administration & dosage*
  • Humans
  • Leukemia, T-Cell / metabolism*
  • Leukemia, T-Cell / pathology*
  • Radiation Tolerance / drug effects
  • Radiation-Protective Agents / administration & dosage
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / metabolism*
  • X-Rays

Substances

  • Free Radical Scavengers
  • Radiation-Protective Agents
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Edaravone
  • Antipyrine