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Abstract
In a series of hydroxyethylaminoalkylaminoanthraquinones (AQ's) based on mitozantrone, 1-AQ (340%) and 1,8-AQ (137%) stimulated basal rate NADPH oxidation (72 + 18pmol min-lmg S9 protein-1) whilst 1,4-AQ, 1,5-AQ and mitozantrone had no effect. A similar trend was observed for O2− generation (measured as nmol acet. cyt c reduction min-1 mg protein-1) by these compounds in MCF-7 S9 fraction: 1-AQ (9.5) and 1,8-AQ (7.9), whilst 1,5-AQ, 1,4-AQ and mitozantrone showed no significant effect. All the AQs including mitozantrone were cytotoxic to MCF-7 cells in a dose dependent manner with EC50 values as follows: 1-AQ (0.01 μm) > doxorubicin (0.4μM) > mitozantrone (0.6μM) > 1,8-AQ (2.O μM) > 1,5-AQ (4.0μM) > 1,4-AQ (8,0 μM). Thus the redox active AQs were also the most cytotoxic. Mitozantrone however was not redox active but was more cytotoxic than all but 1-AQ hence it would appear that factors other than free radical generation contribute to the antitumor activity of this group of compounds.