Quercetin Iron (III) Complex Enhances Radiation-Induced Cell Death in Human Erythroleukemic Cell Lines by Increasing the Generation of Intracellular ROS

Quercetin iron (III) complex (IronQ) is a paramagnetic agent which exhibits several biological effects. Despite extensive studies about quercetin metal complex, the role of complexes to enhance the effect of radiation still remains unexplored. To this end, we determined whether and how IronQ sensitizes cancer cells to Ionizing Radiation (IR). Doxorubicin resistant leukemic cells (K562/Adr) and their parental cell lines (K562) were used in this study. After treated with IronQ and radiation exposure (1-6 Gy), clonogenic survival assay, apoptosis, cell cycle distribution, acidic vesicular organelle staining and intracellular Reactive Oxygen Species (ROS) generation were evaluated. Combined treatment of IronQ with radiation significantly reduced the cell survival rate in both cell lines compared to radiation exposure alone or the control group. The mechanism underlying the cell growth rate inhibition of IronQ with IR was inducing cell arrest at G2/M phase. Moreover, IronQ pretreatment enhanced radiation-induced apoptosis in both cell lines with a greater efficacy in sensitive cell. Interestingly, increased intracellular ROS and accumulation of Acridine Orange (AO) in acidic organelle compartments in response to IronQ treatment combined with IR were observed 24 h post-treatment. In the context of our present findings demonstrating that IronQ in combination with radiation potentially improves the radiotherapeutic efficacy, the obtained results serve as a new strategy in the development of theranostic medicine.