Differential toxic mechanisms of 2-deoxy-D-glucose versus 2-fluorodeoxy-D-glucose in hypoxic and normoxic tumor cells

Antioxid Redox Signal. 2007 Sep;9(9):1383-90. doi: 10.1089/ars.2007.1714.


The dependence of hypoxic tumor cells on glycolysis as their main means of producing ATP provides a selective target for agents that block this pathway, such as 2-deoxy-D-glucose (2-DG) and 2-fluoro-deoxy-D-glucose (2-FDG). Moreover, it was demonstrated that 2-FDG is a more potent glycolytic inhibitor with greater cytotoxic activity than 2-DG. This activity correlates with the closer structural similarity of 2-FDG to glucose than 2-DG, which makes it a better inhibitor of hexokinase, the first enzyme in the glycolytic pathway. In contrast, because of its structural similarity to mannose, 2-DG is known to be more effective than 2-FDG in interfering with N-linked glycosylation. Recently, it was reported that 2-DG, at a relatively low dose, is toxic to certain tumor cells, even under aerobic conditions, whereas 2-FDG is not. These results indicate that the toxic effects of 2-DG in selected tumor cells under aerobic conditions is through inhibition of glycosylation rather than glycolysis. The intention of this minireview is to discuss the effects and potential clinical impact of 2-DG and 2-FDG as antitumor agents and to clarify the differential mechanisms by which these two glucose analogues produce toxicity in tumor cells growing under anaerobic or aerobic conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaerobiosis
  • Cell Hypoxia / physiology*
  • Deoxyglucose / toxicity*
  • Glycolysis
  • Humans
  • Models, Biological
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Oxygen Consumption / drug effects


  • Deoxyglucose