Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype.

BACKGROUND

Recent studies suggest that the gene for manganese superoxide dismutase (MnSOD) is a candidate tumor-suppressor gene. The present study was designed to study the effect of overexpression of MnSOD on cultured human prostate carcinoma cells.

METHODS

DU145 human prostate carcinoma cells were transfected with the cDNA for manganese superoxide dismutase (MnSOD), and two clones overexpressing MnSOD activity were subsequently characterized by comparison with parental and plasmid control-transfected cells.

RESULTS

One clone overexpressing MnSOD had no change in other antioxidant enzymes (AEs) (nonadapted), while a second clone showed an increase in catalase activity (adapted). Sensitivity of parental, plasmid control-transfected, and MnSOD cDNA-transfected cells to agents that generate oxidative stress correlated with AE profiles. Both clones overexpressing MnSOD activity showed increased reactive oxygen species levels under basal cell culture conditions. Both clones overexpressing MnSOD activity showed inhibition of cell growth in vitro and in vivo compared with parental and plasmid control-transfected cells. Flow cytometry studies using mitochondrial-specific probes showed equal mitochondrial mass in all cell lines, but altered mitochondrial membrane potential in MnSOD-overexpressing clones compared with parental or plasmid control-transfected cells.

CONCLUSIONS

Our results suggest novel mechanisms by which MnSOD overexpression may modulate the malignant phenotype, with potential applications in developing new therapies for prostate cancer.