Glioblastomas are notorious for their resistance to ionizing radiation and
chemotherapy. We hypothesize that this resistance to ionizing radiation is due, in part, to alterations in
antioxidant enzymes. Here, we show that rat and human
glioma cells overexpress the
antioxidant enzyme peroxiredoxin II (Prx II).
Glioma cells in which Prx II is decreased using
shRNA exhibit increased hyperoxidation of the remaining cellular Prxs, suggesting that the redox environment is more oxidizing. Of interest, decreasing Prx II does not alter other
antioxidant enzymes (i.e.,
catalase, GPx, Prx I, Prx III, CuZnSOD, and MnSOD). Analysis of the redox environment revealed that decreasing Prx II increased intracellular
reactive oxygen species in 36B10 cells; extracellular levels of H(2)O(2) were also increased in both C6 and 36B10 cells. Treatment with H(2)O(2) led to a further elevation in intracellular
reactive oxygen species in cells where Prx II was decreased. Decreasing Prx II expression in
glioma cells also reduced clonogenic cell survival following exposure to ionizing radiation and H(2)O(2). Furthermore, lowering Prx II expression decreased intracellular
glutathione and resulted in a significant decline in
glutathione reductase activity, suggesting a possible mechanism for the observed increased sensitivity to oxidative insults. Additionally, decreasing Prx II expression increased cell cycle doubling times, with fewer cells distributed to S phase in C6
glioma cells and more cells redistributed to the most radiosensitive phase of the cell cycle, G2/M, in 36B10
glioma cells. These findings support the hypothesis that inhibiting Prx II sensitizes
glioma cells to oxidative stress, presenting Prxs as potential therapeutic targets.