Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells.

Abstract

In recent years, cellular redox environment gained significant attention as a critical regulator of cellular responses to oxidative stress. Cellular redox environment is a balance between production of reactive oxygen species and their removal by antioxidant enzymes. We investigated the hypothesis that mitochondrial antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Vector-control and manganese superoxide dismutase (MnSOD) overexpressing human pancreatic cancer cells were irradiated and assayed for cell survival and activation of the G(2)-checkpoint pathway. Increased MnSOD activity significantly increased cell survival following irradiation with 6 Gy of gamma-radiation (p < 0.05). The MnSOD overexpressing irradiated cells also revealed 3-4 folds increase in the percentage of G(2) cells compared to irradiated vector-control. Furthermore, MnSOD overexpressing irradiated cells exhibited increased loss of phosphorylated histone H2AX protein levels. The radiation-induced increase in cyclin B1 protein levels in irradiated vector-control cells was suppressed in irradiated MnSOD overexpressing cells. Mitochondria-targeted catalase overexpression increased the survival of irradiated cells. These results support the hypothesis that mitochondrial antioxidant enzyme activity and mitochondria-generated reactive oxygen species-signaling (superoxide and hydrogen peroxide) could regulate radiation-induced G(2) checkpoint activation and radioresistance in human pancreatic cancer cells.

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@article{Fisher2008MitochondriatargetedAE, title={Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells.}, author={Carolyn J Fisher and Prabhat C. Goswami}, journal={Cancer biology & therapy}, year={2008}, volume={7 8}, pages={1271-9} }