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Metabolic regulation of tumor cells exposed to different oxygenated polycyclic aromatic hydrocarbons

Rui Gao1, Zihao Jiang2, Xiuyu Wu3

  • 1School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, PR China; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.

The Science of the Total Environment
|October 15, 2023
PubMed

Insights

Certain oxygenated polycyclic aromatic hydrocarbons (OPAHs) promote cancer by affecting cell movement and blood vessel growth. Their tumor-promoting effects are linked to oxidative stress and altered glutathione metabolism.

Area of Science:

  • Environmental Chemistry
  • Toxicology
  • Molecular Biology

Background:

  • Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are derivatives of polycyclic aromatic hydrocarbons with oxygen-containing functional groups.
  • OPAHs are known to induce oxidative stress and mutations, but their carcinogenic and metabolic effects are not well understood.
  • Limited research exists on the specific mechanisms by which OPAHs contribute to cancer development.

Purpose of the Study:

  • To investigate the carcinogenic effects of four different OPAHs.
  • To explore the role of OPAHs in promoting cell invasion, metastasis, and angiogenesis.
  • To understand the relationship between OPAH carcinogenicity and their impact on cellular metabolism, particularly glutathione metabolism.

Main Methods:

  • Analysis of the carcinogenic effects of four OPAHs: 9-fluorenone (FLO), 9,10-anthraquinone (AQ), 7,12-benz(a)anthraquinone (BAQ), and 1,8-naphthalic anhydride (NAD).
  • Evaluation of OPAH-induced epithelial-mesenchymal transition (EMT) to assess cell invasion and metastasis.
  • Measurement of endothelial cell angiogenesis by analyzing the expression of vascular endothelial growth factor (VEGF), angiopoietin (ANG), and platelet-derived growth factor (PDGF).
  • Integration of metabolomic analysis to link OPAH effects to metabolic pathways, focusing on glutathione metabolism and oxidative stress.

Main Results:

  • 9-fluorenone (FLO), 9,10-anthraquinone (AQ), and 7,12-benz(a)anthraquinone (BAQ) significantly promoted cell invasion and metastasis via EMT.
  • These three OPAHs also induced endothelial cell angiogenesis by altering the expression of VEGF, ANG, and PDGF.
  • 1,8-naphthalic anhydride (NAD) did not exhibit significant carcinogenic effects.
  • Metabolomic analysis revealed that the tumor-promoting activities of OPAHs are associated with their impact on the metabolome, especially glutathione metabolism and oxidative stress.

Conclusions:

  • Specific OPAHs (FLO, AQ, BAQ) possess carcinogenic properties, driving key processes like metastasis and angiogenesis.
  • The carcinogenic effects of OPAHs are mechanistically linked to their influence on cellular oxidative stress and glutathione metabolism.
  • These findings provide a foundation for further research into OPAH carcinogenicity and risk assessment.
Keywords:
AngiogenesisEMTMetabolic regulationOxygenated polycyclic aromatic hydrocarbonsTumor

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