Role of the glutathione-glutathione peroxidase cycle in the cytotoxicity of the anticancer quinones.

Journal Article (Journal Article;Review)

Recent studies have suggested that the selenoenzyme glutathione peroxidase, in the presence of reducing equivalents from the tripeptide glutathione, is responsible for detoxifying hydrogen peroxide and lipid hydroperoxides generated as a consequence of the cyclic reduction and oxidation of quinone-containing anticancer agents including doxorubicin, daunorubicin, mitomycin C, diaziquone, and menadione. Alterations in the intracellular levels of glutathione peroxidase or glutathione can significantly affect the activity of these drugs against human tumor cells and the expression of their normal tissue toxicity, especially with respect to the heart. Furthermore, augmentation of the glutathione peroxidase pathway appears to render certain human tumor cells relatively resistant to the anticancer quinones; therefore, the glutathione peroxidase system may, at least in part, modulate certain forms of acquired drug resistance in man. Thus, the glutathione peroxidase cycle appears to play a central role in maintaining intracellular peroxide homeostasis during quinone-induced oxidative stress.

Full Text

Duke Authors

Cited Authors

  • Doroshow, JH; Akman, S; Chu, FF; Esworthy, S

Published Date

  • 1990

Published In

Volume / Issue

  • 47 / 3

Start / End Page

  • 359 - 370

PubMed ID

  • 2290853

International Standard Serial Number (ISSN)

  • 0163-7258

Digital Object Identifier (DOI)

  • 10.1016/0163-7258(90)90062-7


  • eng

Conference Location

  • England