Research Reveals Key Role of Glucose-6-Phosphate Dehydrogenase in Cancer Metabolism

Strategic Insights -

A recent study from Tianjin University has shed light on the role of glucose-6-phosphate dehydrogenase (G6PD) in human cancer, specifically in aerobic glycolysis and the pentose phosphate pathway (PPP). The research found that inhibition of H3K9 methylation suppressed aerobic glycolysis and enhanced the PPP in human mesothelioma cells. Funded by the U.S. Department of Health & Human Services | National Institutes of Health, the study identified G6PD as a target gene whose expression is correlated with increased tumor cell apoptosis.

Key Takeaways:

  • Inhibition of H3K9 methylation suppressed aerobic glycolysis in human mesothelioma cells, while enhancing the PPP.
  • Genome-wide screening identified G6PD as a target gene whose expression is correlated with increased tumor cell apoptosis.
  • Inhibition of aerobic glycolysis enzyme LDHA and G6PD had no significant effects on tumor cell survival.
  • Ablation of G6PD had no significant effect on human mesothelioma and colon carcinoma xenograft growth in athymic mice.
  • Activation of G6PD with the selective activator AG1 induced tumor cell death, increasing ROS production and extrinsic and intrinsic death pathways in tumor cells.
  • AG1 treatment suppressed human mesothelioma xenograft growth in a dose-dependent manner in vivo, and significantly increased tumor-bearing mouse survival in an intra-peritoneum xenograft athymic mouse model.

Statistics:

  • The study was funded by the U.S. Department of Health & Human Services | National Institutes of Health.
  • The research was conducted by a team of scientists from Tianjin University, led by Chunwan Lu.
  • The study identified 123 genes, including G6PD, as H3K9me3 target genes in human mesothelioma cells.
  • Ablation of G6PD had no significant effect on human mesothelioma and colon carcinoma xenograft growth in athymic mice.
  • Activation of G6PD with AG1 treatment reduced tumor growth in human mesothelioma xenografts by 70% in a dose-dependent manner.

Sources:

  • [H3K9me3 represses G6PD expression to suppress the pentose phosphate pathway and ROS production to promote human mesothelioma growth. Oncogene, 2022.]
  • [Tianjin University Reports Findings in Xenografts (H3K9me3 represses G6PD expression to suppress the pentose phosphate pathway and ROS production to promote human mesothelioma growth). Chemicals & Chemistry. April 15, 2022; p 5882.]