Role of NAD(P)H:quinone oxidoreductase (NQO1) in apoptosis induction by aziridinylbenzoquinones RH1 and MeDZQ.
We aimed to characterize the role of NAD(P)H:quinone oxidoreductase (NQO1) in apoptosis induction by antitumour quinones RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) and MeDZQ (2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone). Digitonin-permeabilized FLK cells catalyzed NADPH-dependent single- and two-electron reduction of RH1 and MeDZQ. At equitoxic concentrations, RH1 and MeDZQ induced apoptosis more efficiently than the nonalkylating duroquinone or H(2)O(2). The antioxidant N,N'-diphenyl-p-phenylene diamine, desferrioxamine, and the inhibitor of NQO1 dicumarol, protected against apoptosis induction by all compounds investigated, but to a different extent. The results of multiparameter regression analysis indicate that RH1 and MeDZQ most likely induce apoptosis via NQO1-linked formation of alkylating species but not via NQO1-linked redox cycling.
Nemeikaite-Ceniene
Ausra
A
Institute of Immunology of Vilnius University, Vilnius, Lithuania.
Dringeliene
Aldona
A
Sarlauskas
Jonas
J
Cenas
Narimantas
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001388:Aziridines / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*
C117776:2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone; D001388:Aziridines; D016227:Benzoquinones; D045304:Cytochromes c; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human