Metabolomic dynamics of the arsenic-transformed bronchial epithelial cells and the derived cancer stem-like cells
| Autor: | Akimasa Seno, Fei Chen, Yao Fu, Yiran Qiu, Bandar Almutairy, Lingzhi Li, Wenxuan Zhang, Chitra Thakur, Priya Wadgaonkar, Zhuoyue Bi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
inorganic chemicals
cancer stem cells chemistry.chemical_element Bronchi Applied Microbiology and Biotechnology Metabolomics Cell Line Tumor medicine cancer Humans Molecular Biology Ecology Evolution Behavior and Systematics Arsenic Chemistry Dynamics (mechanics) arsenic Cancer Epithelial Cells Cell Biology medicine.disease metabolomics Carcinogens Environmental Cell Transformation Neoplastic Cancer research Neoplastic Stem Cells metabolism Metabolic Networks and Pathways Developmental Biology Research Paper |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Accumulating evidence indicates a carcinogenic role of environmental arsenic exposure, but mechanisms on how arsenic fosters malignant transformation of the normal cells are not fully established. By applying untargeted global metabolomics approach, we now show that arsenic is highly capable of perturbing the intracellular metabolic programs of the human bronchial epithelial cells, some of which are prominent hallmarks of cancer cell metabolism. To understand the spatiotemporal patterns of arsenic regulation on multiple metabolic pathways, we treated the cells with environmentally relevant concentration of arsenic, 0.25 μM, consecutively for 6 weeks to 24 weeks, and found that arsenic prompted heme metabolism, glycolysis, sphingolipid metabolism, phospholipid catabolism, protein degradation, and cholesterol breakdown constitutively, but inhibited metabolism of uracil-containing pyrimidine, carnitine, serotonin, polyamines, and fatty acid β-oxidation. A strong inhibition of all metabolites in mitochondrial tricarboxylic acid (TCA) cycle was noted in the cells treated with As3+ for 6 to 13 weeks. However, the metabolites in the earlier, but not the later steps of TCA cycle, including citrate, aconitate and isocitrate, were induced at 16 weeks through 24 weeks of arsenic treatment. This comprehensive metabolomics analysis provides new insights into metabolic perturbation by arsenic and may lead to more precise indications of arsenic in molecular carcinogenesis. |
| Databáze: | OpenAIRE |
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