Iodinated contrast agents decrease the activity of multidrug resistance protein, cell migration, and induce cell...

Iodinated contrast agents are a class of compounds widely used in diagnostic medicine to enhance images of tissues subjected to X-ray techniques. Previous studies have shown that radiocontrast agents are capable of increasing the generation of reactive oxygen species (ROS) and inducing the activation of apoptosis in tumor cells, making these compounds an alternative for cancer treatment. However, there is a lack of studies on their antitumor action in chemotherapy-resistant tumors. Here, we evaluate the cytotoxicity of the iodinated contrast agents TIBA (triiodobenzoic acid) and iohexol in cell lines with different resistance profiles: glioblastoma (A172), parental (K562) and chemotherapy-resistant (Lucena 1) chronic myeloid leukemia. The normal renal epithelial cell line (VERO) was used to evaluate the cytotoxic effects of these compounds in non-tumoral cells. After treatment with TIBA and iohexol at different concentrations, cell viability, ROS, cell death, mitochondrial membrane potential, activity of proteins involved in the multidrug resistance phenotype, glucose influx and migration of glioblastoma cell lines and spheroids were evaluated. Both contrast agents were cytotoxic against Lucena 1 and A172 in a dose-dependent manner. In spheroids, iohexol was the most cytotoxic compound. Furthermore, we demonstrated that cell death induced by contrast agents involves ROS generation. TIBA and iohexol also cause loss of mitochondrial membrane potential in Lucena1 and VERO, inhibit Pgp and MRP1 activity in Lucena 1 and A172, modulate glucose influx and decrease cell migration of A172 cells. We conclude that TIBA and iohexol are promising drugs for adjuvant use in the treatment of chemotherapy-resistant tumors.