Overexpression of Glyoxalase 2 in Human Breast Cancer Cells: Implications for Cell Proliferation and Doxorubicin Resistance

Int J Mol Sci. 2024 Oct 10;25(20):10888. doi: 10.3390/ijms252010888.

Abstract

Glyoxalase 2 (Glo2) is an enzyme of the glyoxalase system whose pathway parallels glycolysis and which aims to remove methylglyoxal (MGO). This study analyzed the possible additional roles of the Glo2 enzyme in breast cancer (MCF7) and non-cancer (HDF) cell lines, investigating its presence at the nuclear level and its potential involvement in cell proliferation and chemotherapy resistance. The results revealed that Glo2 is overexpressed in cancer cells, and its expression is higher during the proliferative (S and G2/M) phases of the cell cycle. The study also examined a post-translational modification (PTM) in which Glo2 could be involved, with S-glutathionylation revealing that Glo2 enhances this PTM in cancer cells both in the cytoplasm and nucleus. Inhibition of Glo2 by p-NCBG resulted in increased sensitivity to doxorubicin, a common chemotherapeutic agent. This suggests that Glo2 increases cancer cell resistance to chemotherapy, potentially through its role in regulating oxidative stress. These results highlight Glo2 as a potential therapeutic target to improve the efficacy of existing treatments.

Keywords: S-glutathionylation; breast cancer cells; glyoxalase 2 (Glo2); nucleus; proliferation; redox metabolism.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Doxorubicin* / pharmacology
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lactoylglutathione Lyase* / genetics
  • Lactoylglutathione Lyase* / metabolism
  • MCF-7 Cells
  • Oxidative Stress / drug effects
  • Protein Processing, Post-Translational
  • Thiolester Hydrolases

Substances

  • Doxorubicin
  • Lactoylglutathione Lyase
  • hydroxyacylglutathione hydrolase
  • Thiolester Hydrolases

Grants and funding

This research received no external funding.