AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?

AMPK (AMP-activated protein kinase) is a sensor of cellular energy status that appears to have arisen during early eukaryotic evolution. In the unicellular eukaryote Saccharomyces cerevisiae, the AMPK orthologue is activated by glucose starvation and is required for the switch from glycolysis (fermentation) to oxidative metabolism when glucose runs low. In mammals, rapidly proliferating cells (including tumour cells) and immune cells involved in inflammation both tend to utilize rapid glucose uptake and glycolysis (termed the Warburg effect or aerobic glycolysis) rather than oxidative metabolism to satisfy their high demand for ATP. Since mammalian AMPK, similar to its yeast orthologue, tends to promote the more energy-efficient oxidative metabolism at the expense of glycolysis, it might be expected that drugs that activate AMPK would inhibit cell proliferation and and hence cancer, as well as exerting anti-inflammatory effects. Evidence supporting this view is discussed, including our findings that AMPK is activated by the classic anti-inflammatory drug salicylate.