Doxorubicin resistance conferred by selective enhancement of intracellular glutathione peroxidase or superoxide dismutase content in human MCF-7 breast cancer cells.

Journal Article (Journal Article)

To examine the role of doxorubicin-stimulated oxyradical formation in tumor cell killing, we introduced glutathione peroxidase (GSH Px) or superoxide dismutase (SOD) into MCF-7 cells by "scrape loading." Control cytoplasmic GSH Px and SOD levels increased from (mean +/- S.E.) 0.37 nmol/min/mg and 0.58 microgram SOD/mg, respectively, to 3.99 or 7.63 nmol/min/mg and 1.40 or 1.83 micrograms SOD/mg after treatment with either 150 or 300 units/ml of GSH Px or 20 or 40 mg/ml SOD. Resistance to doxorubicin was correlated with the level of GSH Px introduced into the MCF-7 cells; a one-hour exposure to 1.75 microM doxorubicin decreased the cloning efficiency of control cells loaded with medium alone to 34%, whereas doxorubicin-treated cells augmented with 150 or 300 units/ml of GSH Px had plating efficiencies of 56 or 86%, P less than 0.05. Introduction of SOD increased MCF-7 resistance to doxorubicin similarly. The heat-inactivated enzymes were not protective. Cells loaded with GSH Px were also resistant to the redox cycling anticancer quinone mitomycin C but not to the redox inactive analogs 5-iminodaunorubicin and mitoxantrone, suggesting that amplification of GSH Px or SOD levels can produce doxorubicin resistance in MCF-7 cells.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • 1991

Published In

Volume / Issue

  • 12-13 Pt 2 /

Start / End Page

  • 779 - 781

PubMed ID

  • 2060850

International Standard Serial Number (ISSN)

  • 8755-0199

Digital Object Identifier (DOI)

  • 10.3109/10715769109145859


  • eng

Conference Location

  • Switzerland