COMBINATION TREATMENT OF HYDROGEN PEROXIDE AND X-RAYS INDUCES APOPTOSIS IN HUMAN PROSTATE CANCER PC-3 CELLS

Purpose: To study the effect of hydrogen peroxide (H2O2) on radiation-induced apoptosis in human prostate cancer PC-3 cells. Methods and Materials: At 4h before the irradiation, PC-3 cells were exposed to 10mM ammonium chloride (NH4Cl) concentrations. Subsequently, cells were exposed to 0.1mM H2O2 just before the irradiations, which were administered with 10-MV X-rays at doses of 10Gy. Results: The percentage of apoptotic cells at 48h after X-irradiation alone, H2O2 alone, and combined X-irradiation and H2O2 was 1.85%, 4.85%, and 28.4%, respectively. With use of combined X-irradiation and H2O2, production of reactive oxygen species (ROS) occurred 4h after the irradiation. This resulted in lysosomal rupturing, mitochondrial fragmentation, and the release of cytochrome c into the cytoplasm from the mitochondria. In contrast, when cells were exposed to NH4Cl before the X-irradiation and H2O2 administration, apoptosis was almost completely suppressed, ROS production did not occur, lysosomal rupture and mitochondrial fragmentation were blocked, and cytochrome c was not released. Conclusions: Hydrogen peroxide strongly enhanced lysosome-dependent radiation-induced apoptosis in human prostate cancer PC-3 cells. A combined use of X-rays and H2O2 can also injure the mitochondrial cytoplasmic organelles and lead to the production of ROS that in and of itself might possibly induce apoptosis. (C) 2009 Elsevier Inc.