3-Bromopyruvate induces expression of antioxidant genes

An alkylating compound, 3-bromopyruvic acid (3-3-bromopyruvic acid (BP)) is a promising anti-cancer agent, potentially able to act on multidrug-resistant cells. Its action has been attributed mainly to inhibition of glycolysis. This compound induces also oxidative stress at a cellular level. The effects of 3-BP on gene expression have not been studied although they may determine the survival of cells exposed to 3-BP. The aim of this paper was to examine the effect 3-BP on gene expression pattern in breast MCF-7 cancer cells. Detection of the differences in gene expression was performed using microarrays and dysregulated genes were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Exposure of cells to 100 µM 3-BP for 6, 12 and 24 increased expression and diminished expression of 39 and 6 genes, respectively. Among the induced genes, 22 belong to general cellular stress response genes, maintenance genes involved in redox homeostasis, responding to oxidative stress (among them metallothioneins, low-molecular-weight thiol homeostasis enzymes and genes coding for NAD(P)H-dependent oxidoreductases operating on complex organic substrates, including aldo-keto reductases). These results demonstrate that transient oxidative stress in cells exposed to 3-BP is followed by antioxidant response.