Metabolomic dynamics of the arsenic-transformed bronchial epithelial cells and the derived cancer stem-like cells

Yao Fu, Zhuoyue Bi, Lingzhi Li, Priya Wadgaonkar, Yiran Qiu, Bandar Almutairy, Wenxuan Zhang, Akimasa Seno, Chitra Thakur, Fei Chen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)301-314
Number of pages14
JournalInternational Journal of Biological Sciences
Volume18
Issue number1
DOIs
Publication statusPublished - 2022
Externally publishedYes

Keywords

  • arsenic
  • cancer
  • cancer stem cells
  • metabolism
  • metabolomics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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