Effect of artificial electron acceptors on the cytotoxicity of mitomycin C and doxorubicin in human lung tumor cells

Hiskias G. Keizer, Sandra J. De Leeuw, Johan Van Rijn, Herbert M. Pinedo, Hans Joenje

Research output: Contribution to journalArticlepeer-review

Abstract

The cytotoxicities of mitomycin C (MMC) and doxorubicin (DOX) have been proposed to depend on intracellular reduction by reduced flavoproteins. We investigated whether MMC- and DOX-induced cytotoxicity could be inhibited by competing for electrons from reduced flavoproteins by the artificial electron acceptors phenazine methosulfate (PMS), menadione (MEN) and methylene blue (MB). In intact SW-1573 human lung tumor cells these compounds proved to be excellent electron acceptors, as judged from their capacity to induce high levels of cyanide-resistant respiration. In addition, PMS, MEN and MB were found to decrease the cytotoxicity of MMC, by 90, 63 and 29%, respectively, at concentrations that were themselves completely nontoxic. In contrast, DOX cytotoxicity was not detectably affected. These results suggest that in SW-1573 cells flavoprotein-mediated bioreduction is required for the cytotoxic effect of MMC, but not for that of DOX.

Original languageEnglish (US)
Pages (from-to)1113-1118
Number of pages6
JournalEuropean Journal of Cancer and Clinical Oncology
Volume25
Issue number7
DOIs
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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