Study of the cytotoxic effects of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MeDZQ) in mouse hepatoma cells.

Abstract

A number of quinones have been shown to be efficient anticancer agents. However, some mechanisms of their action, in particular cell signaling are not well understood. The aim of this study was to partly fill this gap by characterizing the mode of cytotoxicity of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MeDZQ) in malignant mouse hepatoma cells (MH-22A) with regard to the expression and activation of main molecules in MAPK cell signaling pathway. The study revealed unequal roles of MAP kinases in MeDZQ-induced cell death: the compound did not induce significant changes in ERK expression or its phosphorylation; JNK appeared to be responsible for cell survival, however, p38 kinase was shown to be involved in cell death. In order to assess the enzymatic activation mechanisms responsible for the action of MeDZQ, we have also found that the antioxidant N,N'-diphenyl-p-phenylene diamine, the iron-chelating agent desferrioxamine, and DT-diaphorase inhibitor, dicoumarol, partly protected the cells from MeDZQ cytotoxicity. It points to parallel oxidative stress and bioreductive alkylation modes of the cytotoxicity of MeDZQ.