Food grade titanium dioxide induced endoplasmic reticulum stress in colon cells: Comparison between normal and colorectal carcinoma cells

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-10-24 DOI:10.1016/j.tiv.2024.105957

Alina Uribe-García , Estefany I. Medina-Reyes , Carlos A. Flores-Reyes , Alejandro A. Zagal-Salinas , Octavio Ispanixtlahuatl-Meraz , Eduardo Delgado-Armenta , Miguel Santibáñez-Andrade , Cesar M. Flores , Yesennia Sánchez-Pérez , Claudia M. García-Cuéllar , Yolanda I. Chirino

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Abstract

Background

Food-grade titanium dioxide (E171) has been under scrutiny in the last decade since its possible adverse effects; however, the cellular mechanisms underlying E171 toxicity have not been thoroughly described.

Aim

We aimed to compare the effects of E171 on endoplasmic reticulum (ER) homeostasis in normal and cancer colon cells.

Experimental design

We exposed normal, carcinoma, and adenocarcinoma cells to 0.1, 1, 10, 50 and 100 μg/cm² of E171 for 24, 48 and 72 h, and we evaluated ER stress, cell viability, titanium uptake, intracellular calcium concentration, and gene expression related to unfolded protein response (UPR) and chaperone pathways.

Results

Cell viability decreased only after 72 h of exposure to 100 μg/cm² of E171. Adenocarcinoma cells internalized higher titanium amounts than normal and carcinoma cells, but the effects in ER distribution, intracellular calcium concentration, and gene expression were similar among the three cell lines. The expression of UPR and chaperone pathways were downregulated at the lowest concentrations but upregulated at the highest concentrations in the three cell lines.

Conclusion

E171 induces ER stress through alterations in ER distribution, intracellular calcium, and UPR and chaperone protein pathways.

Abstract Image

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食品级二氧化钛诱导结肠细胞内质网应激：正常细胞与结直肠癌细胞的比较

背景：目的：我们旨在比较E171对正常和癌结肠细胞内质网(ER)稳态的影响：我们将正常细胞、癌细胞和腺癌细胞暴露在 0.1、1、10、50 和 100 μg/cm2 的 E171 中 24、48 和 72 小时，并评估了 ER 应激、细胞活力、钛吸收、细胞内钙浓度以及与未折叠蛋白反应（UPR）和伴侣通路相关的基因表达：结果：只有在暴露于 100 μg/cm2 E171 72 小时后，细胞活力才会下降。腺癌细胞内化钛的量高于正常细胞和癌细胞，但三种细胞系的ER分布、细胞内钙浓度和基因表达的影响相似。在三种细胞系中，UPR 和伴侣通路的表达在最低浓度时下调，而在最高浓度时上调：结论：E171通过改变ER分布、细胞内钙、UPR和伴侣蛋白通路诱导ER应激。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.