Abstract

The effect of two quinoline-N-oxide derivatives (2-(4′-nitrostyryl)-quinoline-l-oxide (2-NSQO) and 4-(4′-nitrostyryl)-quinoline-1-oxide (4-NSQO)) on modulation of microsomal NADPH oxidoreductase activity, nicotinamide coenzyme concentrations, and induction of apoptosis in K562 human erythroleukemia cells has been. 4-NSQO at the concentration of (10 μM) and 2-NSQO (10 μM) inhibited the activity of microsomal NADPH cytochrome c reductases in tumor cells by 15 and 50% respectively. Treatment of cells with these compounds for two days resulted in the activation of caspase-9 and caspase-3, the increase in ethidium bromide and 4′,6-diamidino-2-phenylindole (DAPI) fluorescence upon DNA binding, and induction of apoptosis. The latter was preceded by the decrease in intracellular nicotinamide coenzyme concentrations. The results obtained allow considering 4-NSQO (and its structural analogs) as perspective compounds for further experimental studies as antitumor agent with low toxic effect on tissues of an organism.

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