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

Autor: Keizer HG; Department of Radiotherapy, Free University, Amsterdam, The Netherlands., De Leeuw SJ, Van Rijn J, Pinedo HM, Joenje H
Jazyk: angličtina
Zdroj: European journal of cancer & clinical oncology [Eur J Cancer Clin Oncol] 1989 Jul; Vol. 25 (7), pp. 1113-8.
DOI: 10.1016/0277-5379(89)90397-0
Abstrakt: 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.
Databáze: MEDLINE