Aspirin‐induced apoptosis of yeast cells is associated with mitochondrial superoxide radical accumulation and NAD ( P ) H oxidation

In previous studies, we observed that aspirin, a promising cancer‐preventive agent, induces apoptosis in mitochondrial manganese superoxide dismutase ( M n SOD )‐deficient S accharomyces cerevisiae cells grown aerobically in ethanol medium. In this study, we show that aspirin‐induced apoptosis is associated with a significant increase in mitochondrial and cytosolicO 2· −and oxidation of mitochondrial NAD ( P ) H . A concomitant rise in the level of cytosolic C u Z n SOD activity failed to compensate for mitochondrial M n SOD deficiency. However, an observed increase in activity of E scherichia coli F e SOD targeted to the mitochondrial matrix of the M n SOD ‐deficient yeast cells, markedly decreased aspirin‐induced accumulation of mitochondrialO 2· −, significantly increased the mitochondrial NAD ( P ) H level and rescued the apoptotic phenotype. Indeed, recombinant yeast cells expressing E . coli F e SOD behaved in a similar manner to the parent wild‐type yeast cells with native mitochondrial M n SOD activity. Wild‐type cells consistently showed a decrease in mitochondrialO 2· −and an increase in mitochondrial NAD ( P ) H levels in the presence of aspirin in ethanol medium. In fact, in wild‐type cells, our studies supported an antioxidant action of aspirin. Taken together, our results indicate that a pro‐oxidant effect of aspirin occurring predominantly in cells with compromised mitochondrial redox balance may be enough to overcome antioxidant defences resulting in apoptosis, as observed in M n SOD ‐deficient yeast cells.