Methylglyoxal produced by tumor cells through formaldehyde-enhanced Warburg effect potentiated polarization of tumor-associated macrophages

Huijuan Ma, Zhaoqian Ding, Ying Xie, Linyi Li, Dan Li, Kaiyan Lou, Wei Wang, Huan Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Environmental exposure to formaldehyde is known to be associated with cancers and many other diseases. Although formaldehyde has been classified as a group I carcinogen, the molecular mechanisms of its carcinogenicity are still not fully understood. Formaldehyde is also involved in the folate-driven one‑carbon metabolism, and excess amount of formaldehyde was found to interfere with other metabolic pathways including glycolysis, which can enhance Warburg effect and induce immunosuppression in tumor microenvironment. Therefore, different tumor cells and THP-1 derived macrophages were utilized to explore the metabolism-related effects induced by formaldehyde at environmentally relevant concentrations. Significant increases of glucose uptake, glycolysis levels, HIF-1α signaling and methylglyoxal production were observed in tumor cells treated with 20 and 50 μM formaldehyde for 24 h, and the overproduced methylglyoxal in the conditioned medium collected from the tumor cells treated with formaldehyde triggered macrophage polarization towards M2 cells. Myricetin, a flavonol scavenging methylglyoxal, reversed the polarization of macrophages induced by methylglyoxal at 50 μM. These results not only provided essential evidences to reveal the molecular mechanisms of Warburg effect and metabolism-related immunosuppression related to formaldehyde exposure, but also indicated that methylglyoxal could be utilized as a target for therapeutic treatment or prevention of formaldehyde-induced immunotoxicity.

Original languageEnglish (US)
Article number115910
JournalToxicology and Applied Pharmacology
Volume438
DOIs
StatePublished - Mar 1 2022
Externally publishedYes

Keywords

  • Formaldehyde
  • HIF-1α
  • Methylglyoxal
  • Polarization
  • Tumor-associated macrophages
  • Warburg effect

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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