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Updated: Jul 21, 2026
Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy
Published on: September 16, 2019
Iodinated contrast agents decrease the activity of multidrug resistance protein, cell migration, and induce cell
Jessica Sodré Silva de Abreu1, Morgana Teixeira Lima Castelo-Branco2, Janaina Fernandes1
1NUMPEX-BIO, Universidade Federal do Rio de Janeiro, Duque de Caxias, Rio de Janeiro, Brazil.
Abstract:
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.
Insights
Iodinated contrast agents like TIBA and iohexol show promise as cancer treatments. These agents exhibit cytotoxicity against chemotherapy-resistant cancer cells by inducing reactive oxygen species (ROS) and apoptosis.
Area of Science:
- Oncology
- Radiology
- Biochemistry
Background:
- Iodinated contrast agents (ICAs) are used in medical imaging.
- Previous research indicates ICAs can induce tumor cell death via reactive oxygen species (ROS) and apoptosis.
- Limited data exists on ICA efficacy against chemotherapy-resistant cancers.
Purpose of the Study:
- To investigate the cytotoxic effects of TIBA (triiodobenzoic acid) and iohexol on chemotherapy-resistant cancer cell lines.
- To explore the mechanisms of action, including ROS generation, apoptosis, and multidrug resistance modulation.
- To assess the potential of ICAs as adjuvant therapy for resistant tumors.
Main Methods:
- Cytotoxicity assays were performed on glioblastoma (A172), chronic myeloid leukemia (K562, Lucena 1), and normal renal (VERO) cell lines.
- Evaluated cell viability, ROS production, apoptosis, mitochondrial membrane potential, Pgp/MRP1 activity, glucose influx, and cell migration.
- Utilized cell lines with varying resistance profiles, including chemotherapy-resistant Lucena 1.
Main Results:
- Both TIBA and iohexol demonstrated dose-dependent cytotoxicity against Lucena 1 and A172 cells.
- Iohexol exhibited the highest cytotoxicity in spheroid models.
- Contrast agent-induced cell death was linked to ROS generation, mitochondrial dysfunction, and inhibition of multidrug resistance proteins (Pgp, MRP1).
- TIBA and iohexol reduced glucose influx and glioblastoma cell migration.
Conclusions:
- TIBA and iohexol possess significant cytotoxic potential against chemotherapy-resistant cancer cells.
- These agents offer a promising avenue for adjuvant cancer therapy, particularly in resistant malignancies.
- The mechanism involves ROS generation and modulation of key cellular processes related to resistance and proliferation.
