EUROPEAN RADIATION RESEARCH 2012

Hydrogen peroxide enhances radiation-induced apoptosis in PC-3 human prostate cancer cell line under hypoxic conditions

18 Oct 2012, 16:44

1m

Poster Hall (Vietri sul Mare)

poster preferred Modulation of Radiosensitivity Poster Session 3

Speaker

Dr Shinji Kariya (Department of Diagnostic Radiology and Radiation Oncology, Kochi Medical School)

Description

Purpose: We previously reported that hydrogen peroxide (H2O2) strongly enhanced radiation-induced apoptosis in PC-3 human prostate cancer cell line, that this apoptosis was lysosome dependent, and that mitochondria existed downstream of lysosomes in the apoptotic pathway (IJROBP75: 449-454, 2009). In this study, we studied how H2O2 affected radiation-induced apoptosis in the PC-3 human prostate cancer cell line under hypoxic conditions. Materials and Methods: PC-3 cells were maintained in a humidified incubator at 37 degrees C under either hypoxic conditions (1% O2) or normoxic conditions (21% O2). Subsequently, the PC-3 cells were exposed to 0.1 mM H2O2 just before the irradiation of 10 Gy, which were administered with 10-MV X-rays. The percentage of apoptotic cells was determined by flow cytometry. Detection of apoptotic cells, ROS production, and morphemic changes of lysosomes and mitochondria was examined using a CCD camera-equipped fluorescence microscope. Results: Also under hypoxic conditions, H2O2 enhanced radiation-induced apoptosis in the PC-3 human prostate cancer cell line. In addition, the proportions of apoptotic cells with X-rays of 10 Gy and 0.1 mM H2O2 under hypoxic conditions were higher than the proportions of apoptotic cells only with X-rays of 10 Gy under normoxic conditions. As is the case with combination treatment of X-rays and H2O2 under normoxic conditions, long term production of ROS, lysosomal rupturing, and mitochondrial fragmentation were observed under hypoxic conditions. Immediately after administration of H2O2 into the medium, O2 partial pressure of the medium in which PC-3 cells were cultured under hypoxic conditions increased. However, the average O2 partial pressure increase in the medium after 7 minutes of the administration of 0.1 mM H2O2 was a mere 3.6 mmHg. Meanwhile, the activation of glutathione peroxidase in the PC-3 cells under hypoxic conditions decreased. Conclusion: H2O2 decreased the activation of glutathione peroxidase in the hypoxic PC-3 cells and may have led to prevent the removal of the hydroxyradical generated by irradiation, ruptured lysosome, etc.. In conclusion, it was suggested that these phenomena were some of the reasons why H2O2 enhanced radiation-induced apoptosis in the PC-3 human prostate cancer cell line under hypoxic conditions.