[Cellular mechanisms of induction of apoptosis in human erythroleukaemic K562 cells line treated by quinoline-N-oxide derivatives].
We have studied the influence of 2-(4'-nitrostyryl)-quinoline-1-oxide (2-NSQO) and 4-(4'-nitrostyryl)-quinoline-1-oxide (4-NSQO) on modulation activity of microsomal NADPH-oxidoreductases, concentration of nicotinamide enzymes and induction of apoptosis in human erythroleukaemic K562 cells. It was shown, that activity of microsomal NADPH-cytochrome c-reductases in cancer cells was inhibited by 10 microM 4-NSQO (15%), and 10 microM 2-NSQO (50%). Treatment of cells with these reagents for two days, was accompanied by caspases-9 and -3 activation, rise of EtBr and DAPI fluorescence related to DNA binding and induction of apoptosis. Apoptosis was preceded by the decrease of concentration of nicotinamide enzymes. Thus 4-NSQO is a promising compound for further experimental trials as an anticancer drug with low toxic action on the tissues of organism.
Volkova
T O
TO
Zykina
N S
NS
Malysheva
I E
IE
Nemova
N N
NN
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D020014:K562 Cells; D008861:Microsomes / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*
C512403:2-(4'-nitrostyryl)-quinoline-1-oxide; C512404:4-(4'-nitrostyryl)-quinoline-1-oxide; D061945:Caspase Inhibitors; D003497:Cyclic N-Oxides; D005456:Fluorescent Dyes; D011804:Quinolines; D009243:NAD; D015112:4-Nitroquinoline-1-oxide; D045304:Cytochromes c; D009245:NADH Dehydrogenase; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases