The Warburg Effect: Why and How Do Cancer Cells Activate Glycolysis in the Presence of Oxygen?

Miguel      Lopez-Lazaro

Abstract

Cells can obtain energy through the oxygen-dependent pathway of oxidative phosphorylation (OXPHOS) and through the oxygen-independent pathway of glycolysis. Since OXPHOS is more efficient in generating ATP than glycolysis, it is recognized that the presence of oxygen results in the activation of OXPHOS and the inhibition of glycolysis (Pasteur effect). However, it has been known for many years that cancer cells and non-malignant proliferating cells can activate glycolysis in the presence of adequate oxygen levels (aerobic glycolysis or Warburg effect). Accumulating evidence suggests that the persistent activation of aerobic glycolysis in tumor cells plays a crucial role in cancer development; the inhibition of the increased glycolytic capacity of malignant cells may therefore represent a key anticancer strategy. Although some important knowledge has been gained in the last few years on this growing field of research, the basis of the Warburg effect still remains poorly understood. This communication analyzes why cancer cells switch from OXPHOS to glycolysis in the presence of adequate oxygen levels, and how these cells manage to avoid the inhibition of glycolysis induced by oxygen. Several strategies and drugs that may interfere with the glycolytic metabolism of cancer cells are also shown. This information may help develop anticancer approaches that may have clinical relevance.

Keywords: Aerobic glycolysis, glycolysis inhibitors, metabolism, dysoxic metabolism, hypoxia-inducible factor 1, reactive oxygen species, hydrogen peroxide, superoxide anion