Effect of Hyperthermia on self-renewality of prostate cancer stem cells

Introduction: Prostate cancer (PCa) is the most prevalent malignant tumor in the male population worldwide and it is the second leading cause of cancer-related death in males. PCa is almost incurable due to the resistance of PCa to conventional treatments. Cancer stem cells (CSCs) theory suggests that a small subpopulation of cancer cells is responsible for tumor development, relapse and metastasis. This cells possess self-renewal and give rise to nontumorigenic progeny that make up the bulk of the tumor. Materials and Methods: DU145 cells were cultured in stem cell medium containing serum-free medium to generate floating spheres (prostatospheres) enriched cancer stem cells. Sphere formation is progressively used as a golden method for enriching stem cells. Following monolayer and sphere culture, DU145 cells were treated with different doses of hyperthermia. Hyperthermia was applied at 43 °C for 0, 30, 60 and 90 min in a precision water bath with ± 0.1 C accuracy. The survival and self-renewing of the cells were evaluated by colony formation assay (CFA) and Sphere formation assay (SFA). SFA is based on the self-renewing properties unique to CSCs. CFA is used as a measure of the proliferative potential of cells. The results were compared between monolayer and sphere cells. Results: The results show that in both monolayer and Sphere cultures, Survival Fraction (CFA) decreases with the increase of heating time. Prolonged hyperthermia can affect the survival. Results of Survival Fraction (CFA) in equal durations of hyperthermia treatment were not significantly different between monolayer cells and Sphere cells. For both cultures Survival Fraction (SFA) decrease with the increase of hyperthermia exposure time. Results of Survival Fraction (SFA) after 90 min of hyperthermia treatment were significantly different between monolayer cells and Sphere cells. Conclusion: Hyperthermia is a promising approach which is utilized alone or in combination with radiotherapy and/or chemotherapy for the treatment of a variety of tumors. Due to the relative resistance of CSCs to therapy, determination and characterization of thermoresistance of CSCs in the prostate tumor is the key to develop more efficient therapeutic strategies.