Abstract
BackgroundAluminum (Al) is toxic to animals and humans. The most common sources of human exposure to Al are food and beverages. The intestinal epithelium is the first barrier against Al-induced toxicity. In this study, HT-29, a human colon cancer cell line, was selected as an in vitro model to evaluate the Al-induced alteration in metabolomic profiles and explore the possible mechanisms of Al toxicity.MethodsMTT assay was performed to determine the half-maximal inhibitory concentration of Al ions. Liquid chromatography-mass spectrometry (LC-MS) was used for metabolomic analysis, and its results were further confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) of nine selected genes.ResultsAl inhibited the growth of the HT-29 cells, and its half-maximal dose for the inhibition of cell proliferation was found to be four mM. This dose was selected for further metabolomic analysis, which revealed that 81 metabolites, such glutathione (GSH), phosphatidylcholines, phosphatidylethanolamines, and creatine, and 17 metabolic pathways, such as the tricarboxylic acid cycle, pyruvate metabolism, and GSH metabolism, were significantly altered after Al exposure. The RT-qPCR results further confirmed these findings.ConclusionThe metabolomics and RT-qPCR results indicate that the mechanisms of Al-induced cytotoxicity in HT-29 cells include cellular apoptosis, oxidative stress, and alteration of lipid, energy, and amino acid metabolism.
Highlights
Aluminum (Al), a metal that is toxic to animals and humans, is ubiquitous in industrialized societies, and human exposure to Al in daily life is inevitable
MTT assay for cell viability The HT-29 cell viability decreased with the increase in Al concentration from 0 to 10 mM (Fig. 1; Dataset S1)
Our results showed decreased intracellular levels of the ketogenic amino acids leucine, tryptophan, and phenylalanine and the glycogenic amino acid glutamate in Al-treated HT-29 cells, consistent with the results of a previous study on human epidermal keratinocytes (Carrola et al, 2016)
Summary
Aluminum (Al), a metal that is toxic to animals and humans, is ubiquitous in industrialized societies, and human exposure to Al in daily life is inevitable. HT-29, a human colon cancer cell line, was selected as an in vitro model to evaluate the Al-induced alteration in metabolomic profiles and explore the possible mechanisms of Al toxicity. Results: Al inhibited the growth of the HT-29 cells, and its half-maximal dose for the inhibition of cell proliferation was found to be four mM This dose was selected for further metabolomic analysis, which revealed that 81 metabolites, such glutathione (GSH), phosphatidylcholines, phosphatidylethanolamines, and creatine, and 17 metabolic pathways, such as the tricarboxylic acid cycle, pyruvate metabolism, and GSH metabolism, were significantly altered after Al exposure. Conclusion: The metabolomics and RT-qPCR results indicate that the mechanisms of Al-induced cytotoxicity in HT-29 cells include cellular apoptosis, oxidative stress, and alteration of lipid, energy, and amino acid metabolism
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