Glutamine metabolism as a potential target for prostate cancer radiosensitization

Tumor relapse associated with increased chemo- and radioresistance is a major problem for prostate cancer patients. Our previous findings suggest that altered amino acid (in particular, glutamine) metabolism can be associated with radioresistance of prostate cancer. The main aim of our project is to investigate the role of glutamine metabolism in the development of prostate cancer radioresistance and to find novel biomarkers to predict radiation treatment outcome. We used isogenic radioresistant cell lines developed from standard prostate cancer cell lines DU145, PC3, 22RV1 and LNCaP and analyzed the following parameters: the differential expression of genes involved in glutamine metabolism, cells’ tumorigenicity, metabolites of Krebs cycle, the amount of reactive oxygen species (ROS) and glutathione in cells, radioresistance of cells and DNA damage after irradiation.
Our findings suggest that glutamine metabolism contributes to prostate tumor cell proliferation, stem cell marker expression, tumorigenicity, oxidative stress, radioresistance and epigenetic changes. The combination of irradiation with inhibition of glutamine metabolism may increase the cytotoxic effects of irradiation in prostate tumor cells. Expression of the proteins involved in glutamine metabolism can be used to predict clinical outcome of prostate cancer patients. The intracellular mechanisms of the differential tumor cell sensitivity to glutamine supplementation are in the focus of ongoing study.