Glutathione‑degrading enzymes in the complex landscape of tumors (Review)

Int J Oncol. 2024 Jul;65(1):72. doi: 10.3892/ijo.2024.5660. Epub 2024 Jun 7.


Glutathione (GSH)‑degrading enzymes are essential for starting the first stages of GSH degradation. These enzymes include extracellular γ‑glutamyl transpeptidase (GGT) and intracellular GSH‑specific γ‑glutamylcyclotransferase 1 (ChaC1) and 2. These enzymes are essential for cellular activities, such as immune response, differentiation, proliferation, homeostasis regulation and programmed cell death. Tumor tissue frequently exhibits abnormal expression of GSH‑degrading enzymes, which has a key impact on the development and spread of malignancies. The present review summarizes gene and protein structure, catalytic activity and regulation of GSH‑degrading enzymes, their vital roles in tumor development (including regulation of oxidative and endoplasmic reticulum stress, control of programmed cell death, promotion of inflammation and tumorigenesis and modulation of drug resistance in tumor cells) and potential role as diagnostic biomarkers and therapeutic targets.

Keywords: ChaC1; GGT; GSH degrading enzyme; tumor.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Endoplasmic Reticulum Stress
  • Gene Expression Regulation, Neoplastic
  • Glutathione* / metabolism
  • Humans
  • Neoplasms* / enzymology
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Oxidative Stress
  • gamma-Glutamylcyclotransferase* / genetics
  • gamma-Glutamylcyclotransferase* / metabolism
  • gamma-Glutamyltransferase* / metabolism


  • Glutathione
  • gamma-Glutamylcyclotransferase
  • gamma-Glutamyltransferase
  • Biomarkers, Tumor

Grants and funding

The present study was supported by the Shanghai Style TCM Inheritance and Innovation Team Building Project (grant no. 2021LPTD-004), Natural Science Foundation of Shanghai (grant nos. 19ZR1457500, 19ZR1460800 and 18ZR1440300) and Research Project of Shanghai Health Commission (grant no. 202140348).