Combining Multiple Omics with Molecular Dynamics Reveals SCP2-Mediated Cytotoxicity Effects of Aflatoxin B1 in SW480 Cells

• Published in: Toxins Vol. 16; no. 9; p. 375
• Main Authors: Chen, Mengting, Wen, Jiaxin, Qiu, Yiyan, Gao, Xinyue, Zhang, Jian, Lin, Yifan, Wu, Zekai, Lin, Xiaohuang, Zhu, An
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-09-2024; MDPI
• Subjects: Aflatoxin B1; Aflatoxin B1 - toxicity; Aflatoxins; Amino acids; Antioxidants; Calcium (mitochondrial); Calcium metabolism; Carcinogenicity; Carcinogens; Cell Line, Tumor; Cell Survival - drug effects; Cell viability; Cytotoxicity; Endoplasmic reticulum; Exposure; Fatty acids; Genes; Genomes; Genomics; Glutathione; Health aspects; Hepatotoxicity; Homeostasis; Humans; intestinal toxicity; Intestine; Lipid metabolism; Lipid Metabolism - drug effects; lipid metabolism disorder; Lipids; Metabolism; Metabolites; Metabolome - drug effects; mitochondrial damage; Molecular dynamics; Molecular Dynamics Simulation; multiple omics; Mycotoxins; Neurotoxicity; Oxidative metabolism; Oxidative stress; Oxidative Stress - drug effects; Proteins; Proteome - drug effects; Proteomes; Proteomics; Toxic diseases; Toxicity; Transcriptome - drug effects; Transcriptomes; China; mitochondrial damage; multiple omics; intestinal toxicity; aflatoxin B1; lipid metabolism disorder; oxidative stress
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins16090375

Aflatoxins belong to a class of mycotoxins, among which aflatoxin B1 (AFB1) has detrimental effects on the health of both animals and humans. It is associated with long-term exposure-induced carcinogenicity, hepatotoxicity, renal toxicity, neurotoxicity, and immunosuppressive properties, resulting in a variety of diseases. The intestine is the first barrier for human exposure to AFB1, but limited investigations have been conducted to clarify the underlying mechanisms of intestinal cytotoxicity. The mechanism of AFB1-induced cytotoxicity was investigated in this study using an integrated approach combining transcriptome, proteome, and metabolome analysis along with molecular dynamics simulation. After exposing SW480 cells to 50 μM AFB1 for 72 h, the transcriptome, proteome, and metabolome exhibited significant enrichment in pathways associated with oxidative stress, fatty acid and lipid metabolism, and glutathione metabolism. The experimental results demonstrated that AFB1 significantly reduces SW480 cells viability, and induces oxidative stress, calcium overload, mitochondrial damage, and lipid metabolism disorders.