Preventive effect of trimidox on oxidative stress in U937 cell line.
Trimidox (3,4,5-trihydroxybenzamidoxime) is one of the most potent ribonucleotide reductase inhibitors, revealing an antitumor effect in several experimental studies. We have examined the effect of trimidox on the induction of cytotoxicity and apoptosis via oxidative stress by typical free radical inducers, hydrogen peroxide (H(2)O(2)), tert-butylhydroperoxide (tBuOOH) or ultraviolet (UV) irradiation in a human diffuse histiocytic lymphoma U937 cell line. Trimidox showed strong radical scavenging activity by the DPPH reduction assay. The 50% rate inhibited the DPPH reduction concentration of trimidox, and its derivates didox, or gallic acid were 8.8 microM, 117.5 microM, or 41.8 microM, respectively. Induction of cytotoxicity by H(2)O(2) (500 microM) or tBuOOH (100 microM) was concentration-dependently attenuated by incubation with Trimidox (10-150 microM). Trimidox also prevented the effect of UV-induced apoptosis estimated by both nuclear morphological change and DNA fragmentation. This effect was due to inhibition of the production of reactive oxygen species. Moreover, the activity and mRNA expression of catalase, an antioxidant enzyme, was significantly increased by trimidox. These results indicate that trimidox has radical scavenging activity and prevents exogenous oxidative stress and increase in catalase; therefore, trimidox is suggested as an anticancer agent exhibiting potent antioxidant properties in this study.
Kanno
Syu-Ichi
S
Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai, Japan. syu-kan@tohoku-pharm.ac.jp
Kakuta
Mai
M
Kitajima
Yasue
Y
Osanai
Yuu
Y
Kurauchi
Kaori
K
Ohtake
Takaharu
T
Ujibe
Mayuko
M
Uwai
Kouji
K
Takeshita
Mitsuhiro
M
Ishikawa
Masaaki
M
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001550:Benzamidines / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D014466:Ultraviolet Rays / Q000009:adverse effects; D020122:tert-Butylhydroperoxide / Q000633:toxicity
C074761:3,4,5-trihydroxybenzamidoxime; D000975:Antioxidants; D001550:Benzamidines; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide