Dehydroepiandrosterone Augments Sensitivity to γ-Ray Irradiation in Human H4 Neuroglioma Cells Through Down-regulation of Akt signaling.

Running Head; DHEA and radiosensivity in glioma cells. Dehydroepiandrosterone (DHEA) modulates sensitivity to radiation-induced injury in human neuroglioma cells (H4) through effects on Akt signaling by glutathione (GSH)-dependent redox regulation. Previous treatment of H4 cells with DHEA for 18h reduced the γ-ray-induced phosphorylation of Akt, activated p21waf1 synthesis, and up-regulated phosphorylation of Rb independent of p53. These reactions were followed by a decrease in cell number, and an increase in apoptosis and G2/M checkpoint arrest. The suppression of phosphorylation of Akt by DHEA was due to regulation of the dephosphorylation by protein phosphatase 2A (PP2A). DHEA up-regulated the expression of γ-glutamylcysteine synthetase, a rate limiting enzyme of glutathione (GSH) synthesis, and the levels of GSH to maintain PP2A activity. The result