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.
References
Nov 1, 1979·Analytical Biochemistry·B M Jørgensen, H N Rasmussen
Mar 1, 1979·Biochemical Pharmacology·R E TalcottE T Wei
Mar 9, 1985·Lancet·W J HrusheskyJ W Eaton
Dec 1, 1985·Archives of Biochemistry and Biophysics·M W SutherlandH J Forman
Jan 31, 1972·Biochemical and Biophysical Research Communications·M NishikimiK Yagi
Oct 26, 1984·Science·K M TeweyL F Liu
Jun 1, 1982·Archives of Biochemistry and Biophysics·C LindL Ernster
May 1, 1983·Archives of Biochemistry and Biophysics·P L GutiérrezN R Bachur
Nov 22, 1983·Biochimica Et Biophysica Acta·D A Rowley, B Halliwell
Feb 28, 1984·Biochemistry·H EliotC Myers
Jan 1, 1980·Biochemical Pharmacology·T M GuenthnerD W Nebert
Oct 1, 1980·Biochemical Pharmacology·G Powis, P L Appel
May 15, 1982·Biochemical Pharmacology·W E Ross, M C Smith
Jun 1, 1981·Archives of Biochemistry and Biophysics·B A Svingen, G Powis
Jan 1, 1981·Histochemistry·B Henderson, N Loveridge
Jul 3, 1964·Science·V N IYER, W SZYBALSKI
Citations
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·K A MargolinJ H Doroshow
Jan 1, 1995·Investigational New Drugs·M TetefJ H Doroshow
Jan 1, 1995·Journal of Cancer Research and Clinical Oncology·M TetefS Shibata
May 4, 2005·Investigational New Drugs·Dean LimJames H Doroshow
Jan 1, 1990·Pharmacology & Therapeutics·H G KeizerH Joenje
Jun 1, 1992·American Journal of Medical Genetics·L P ten Kate