Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes

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Abstract

The anticancer activity of aziridinyl-quinones is mainly attributed to their NAD(P)H:quinone oxidoreductase 1 (NQO1)-catalyzed two-electron reduction into DNA-alkylating products. However, little is known about their cytotoxicity in primary cells, which may be important in understanding their side effects. We found that the cytotoxicity of aziridinyl-unsubstituted quinones (n = 12) in mice splenocytes with a low amount of NQO1, 4 nmol × mg-1 × min-1, was caused mainly by the oxidative stress. Aziridinyl-benzoquinones (n = 6) including a novel anticancer agent RH1 were more cytotoxic than aziridinyl-unsubstituted ones with the similar redox properties, and their cytotoxicity was not decreased by an inhibitor of NQO1, dicumarol. The possible reasons for their enhanced cytotoxicity are discussed.

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Miliukiene, V., Nivinskas, H., & Čenas, N. (2014). Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes. Acta Biochimica Polonica, 61(4), 833–836. https://doi.org/10.18388/abp.2014_1854

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