Free radical scavenger edaravone suppresses x-ray-induced apoptosis through p53 inhibition in MOLT-4 cells.
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.
Sasano
Nakashi
N
Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Enomoto
Atsushi
A
Hosoi
Yoshio
Y
Katsumura
Yosuke
Y
Matsumoto
Yoshihisa
Y
Shiraishi
Kenshiro
K
Miyagawa
Kiyoshi
K
Igaki
Hiroshi
H
Nakagawa
Keiichi
K
D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology*; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014965:X-Rays
D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077553:Edaravone; D000983:Antipyrine