Functional benefit and molecular mechanism of vitamin C against perfluorooctanesulfonate-associated leukemia

Chemosphere. 2021 Jan:263:128242. doi: 10.1016/j.chemosphere.2020.128242. Epub 2020 Sep 4.

Abstract

Perfluorooctanesulfonate (PFOS) is a persistent pollutant that can induce toxic effects, including leukemia, on blood cells. Vitamin C (VC), a functional nutrient, has been found to possess potent cytoprotective effects. However, there are currently no reports on its ability to treat PFOS-associated leukemia. This study used a molecular networking analysis to reveal the functional action and pharmacological mechanism of VC against PFOS-associated leukemia. The biological informatics findings revealed a total of 17 intersection targets against PFOS-associated leukemia. In addition, seven core-functional targets, including tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), sirtuin 1 (SIRT1), nitric oxide synthase 3 (NOS3), myeloid cell leukemia-1 (MCL1), and telomerase reverse transcriptase (TERT), were screened and identified. Notably, the molecular docking findings indicated that TP53, MAPK1, and ESR1 were potent pharmacological targets of VC against PFOS-associated leukemia. Moreover, the pharmacological functions including biological processes, cell components, and molecular pathways of VC against PFOS-associated leukemia were determined. According to the computational findings, we conclude that VC protects against PFOS-associated leukemia action by suppressing leukemia-associated cell proliferation and tumor growth. The validated genes of TP53, MAPK1, ESR1 may become potential biomarkers for monitoring and treating PFOS-associated leukemia.

Keywords: Leukemia; Molecular mechanism; Network pharmacology; Perfluorooctanesulfonate; Pharmacological targets; Vitamin C.

MeSH terms

  • Alkanesulfonic Acids* / toxicity
  • Ascorbic Acid
  • Fluorocarbons* / toxicity
  • Humans
  • Leukemia* / chemically induced
  • Molecular Docking Simulation
  • Signal Transduction

Substances

  • Alkanesulfonic Acids
  • Fluorocarbons
  • perfluorooctane sulfonic acid
  • Ascorbic Acid