Preventive Effect of Trimidox on Oxidative Stress in U937 Cell Line

• Kanno Syu-ichi

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Kakuta Mai

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Kitajima Yasue

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Osanai Yuu

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Kurauchi Kaori

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Ohtake Takaharu

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Ujibe Mayuko

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Uwai Kouji

  Department of Pharmaceutics, Tohoku Pharmaceutical University

• Takeshita Mitsuhiro

  Department of Pharmaceutics, Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

抄録

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 (H₂O₂), 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 μM, 117.5 μM, or 41.8 μM, respectively. Induction of cytotoxicity by H₂O₂ (500 μM) or tBuOOH (100 μM) was concentration-dependently attenuated by incubation with Trimidox (10—150 μM). 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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 30 (5), 994-998, 2007

  公益社団法人 日本薬学会

キーワード

• trimidox
• antioxidant
• oxidative stress
• apoptosis
• radical scavenging
• catalase

詳細情報

• CRID: 1390282679602226432
• NII論文ID: 110006273305
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.30.994
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 8714576
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8714576
• Web Site: http://www.jstage.jst.go.jp/article/bpb/30/5/30_5_994/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007258024
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可