Radiosensitization of PC3 Prostate Cancer Cells by 5-Thiocyanato-2′-deoxyuridine

SIMPLE SUMMARY: Radiation therapy is one of the main treatments for cancer. However, the success of treatment by radiation therapy is largely dependent on tumor radiosensitivity. To improve therapeutic outcomes, radiation therapy should be combined with the use of a radiosensitizer which enables irradiation at lower doses with higher efficacies. 5-Thiocyanato-2′-deoxyuridine has been reported as a potential radiosensitizer of DNA damage based on advanced radiation chemical studies. In this paper, for the first time, we demonstrate the radiosensitizing properties of this modified nucleoside at the cellular level. The tested analogue increases the sensitivity of prostate cancer cells to ionizing radiation which is, at least partially, related to an increase in the number of DNA double-strand breaks and cell cycle regulation. ABSTRACT: Purpose: The radiosensitizing properties of uracil analogs modified in the C5 position are very interesting in the context of their effectiveness and safety in radiation therapy. Recently, radiation chemical studies have confirmed that 5-thiocyanato-2′-deoxyuridine (SCNdU) undergoes dissociation induced by an excess electron attachment and established this nucleoside as a potential radiosensitizer. In this paper, we verify the sensitizing properties of SCNdU at the cellular level and prove that it can effectively enhance ionizing radiation-induced cellular death. Methods and Materials: Prostate cancer cells were treated with SCNdU and irradiated with X rays. The cytotoxicity of SCNdU was determined by MTT test. Cell proliferation was assessed using a clonogenic assay. Cell cycle analyses, DNA damage, and cell death analyses were performed by flow cytometry. Results: SCNdU treatment significantly suppressed the proliferation and increased the radiosensitivity of prostate cancer cells. The radiosensitizing effect expressed by the dose enhancement factor is equal to 1.69. Simultaneous exposure of cells to SCNdU and radiation causes an increase in the fraction of the most radiosensitive G2/M phase, enhancement of the histone H2A.X phosphorylation level, and apoptosis induction. Finally, SCNdU turned out to be marginally cytotoxic in the absence of ionizing radiation. Conclusions: Our findings indicate that SCNdU treatment enhances the radiosensitivity of prostate cancer cells in a manner associated with the cell cycle regulation, double strand formation, and a slight induction of apoptosis.