Inhibition of plasma membrane NADH dehydrogenase by adriamycin and related anthracycline antibiotics.
Doxorubicin (adriamycin) is cytotoxic to cells, but the biochemical basis for this effect is unknown, although intercalation with DNA has been proposed This study suggests that the cytotoxicity of this drug may be due to inhibition of the plasma membrane redox system, which is involved in the control of cellular growth. Concentrations between 10(-6) - 10(-7) M adriamycin inhibit plasma membrane redox reactions greater than 50%. AD32, a form of adriamycin which does not intercalate with DNA, but is cytotoxic, also inhibits the plasma membrane redox system. Thus, the cytotoxic effects of adriamycin, which limit its use as a drug, may be based on the inhibition of a transplasma membrane dehydrogenase involved in a plasma membrane redox system.
D000818:Animals; D000903:Antibiotics, Antineoplastic; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D003579:Cytochrome Reductases / Q000037:antagonists & inhibitors*; D004317:Doxorubicin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D051379:Mice; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D009279:Naphthacenes / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D004317:Doxorubicin; D009247:NADH, NADPH Oxidoreductases; D003579:Cytochrome Reductases; C014227:ferricyanide reductase; D009245:NADH Dehydrogenase