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The contrast agent 2,3,5-triiodobenzoic acid (TIBA) induces cell death in tumor cells through the generation of reactive oxygen species

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Abstract

The 2,3,5-triiodobenzoic acid (TIBA) is an iodine contrast agent used for visualization of tissue in X-ray techniques. However, TIBA induces physiological complications like increase in oxygen reactive species (ROS), and consequently, contrast-induced nephropathies. TIBA’s antitumor activity was demonstrated in lung cancer, but the subcellular mechanisms involving its activity in tumor cells are still unknown. Thus, the objective of this work was evaluate whether the anti-tumor activity of TIBA involves ROS increase, in tumor lines of non-small cell lung cancer (H460), chronic myeloid leukemia (K562), and its cytotoxicity in normal renal epithelial (VERO). The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay was used for evaluation of cell viability, the H2DCFDA (cell-permeant 2′,7′-dichlorodihydrofluorescein diacetate) fluorescent probe to evaluate ROS induction, cell cycle analysis was performed using flow cytometry to measure cell death, and immunofluorescence with annexin/7-AAD (7-amino-actinomycin D), to assess the association of cell death with the ROS generation. TIBA decreases cell viability in a dose-dependent manner for the H460 and K562. However, VERO cells showed less response to the drug, with 70% viable cells after 72 h of treatment in the highest concentration of the drug. While the tumor cells with only 20% viable cells. Besides, tumor cells exhibited higher DNA fragmentation, compared to the renal line (VERO with 5% of fragmented DNA, H460 with 26%, and 56% in K562). Finally, TIBA-induced ROS increase and apoptosis in all lines, which is significantly decreased after treatment with the antioxidant N-acetyl-cysteine (NAC). These data demonstrate the relationship between the increased cellular oxidative stress and the anti-tumor action of the TIBA.

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Data availability

The datasets generated during and/or analysed during the current study are available in the Figshare repository, https://doi.org/10.6084/m9.figshare.c.5329523.v2.

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Funding

The work was supported by the Research Support Foundation of the State of Rio de Janeiro (Grant Number E-26/201.037/2020).

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  1. Nucleus of Multidisciplinary Research in Biology (Numpex-Bio), Universidade Federal Do Rio de Janeiro (UFRJ), Rio de Janeiro, Duque de Caxias, Brazil

    Jéssica Sodré Silva de Abreu & Janaína Fernandes

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  1. Jéssica Sodré Silva de Abreu
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  2. Janaína Fernandes
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Correspondence to Janaína Fernandes.

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de Abreu, J.S.S., Fernandes, J. The contrast agent 2,3,5-triiodobenzoic acid (TIBA) induces cell death in tumor cells through the generation of reactive oxygen species. Mol Biol Rep 48, 5199–5207 (2021). https://doi.org/10.1007/s11033-021-06524-5

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