Press clipping: Research
New research carried out by Professor Grahame Hardie at the College of Life Sciences could lead to new uses for one of the world's oldest medicines.
Ancient Egyptian manuscripts described the use of extracts of willow bark as a medicine. Willow bark is now known to contain salicylate, made by plants in response to infection.
Aspirin (acetyl salicylate) was developed in the 1890s as a modified form of salicylate that is less irritating to the stomach, but which is rapidly broken down to salicylate following its adsorption.
Professor Hardie has now identified that salicylate switches on the AMP-activated protein kinase (AMPK), an enzyme that he himself originally defined in the 1980s. AMPK acts as a molecular switch that inhibits cell growth and has many effects on metabolism. The new studies, published in the journal Science, have identified that some of the metabolic effects of salicylate are mediated by AMPK.
Professor Hardie said, "Aspirin is one of the most widely used drugs in the world, and arguably the most successful drug ever developed. We have shown that, unlike other aspirin targets, AMPK is only affected by salicylate, the breakdown product of aspirin in the body, and not by aspirin itself.
"Aspirin has many beneficial effects but, despite it being used in humans for over 100 years, we are still finding out how they come about.
“Although further studies are required, our findings raise the possibility that some benefits of aspirin, such as protection against cancer, might be mediated by AMPK. Supporting this idea is the 2005 discovery made by Professor Andrew Morris in Dundee that the diabetes drug metformin, which also switches on AMPK, is another drug that provides protection against cancer.
"Despite its anti-cancer effects, doctors do not recommend that everyone should take aspirin because it can have side effects, including increased risk of stomach bleeding. If we can prove that the anti-cancer effects are mediated by AMPK, then other salicylate-based drugs, with fewer side effects than aspirin, might perhaps be used instead."
The paper was co-authored by Dr Greg Steinberg from McMaster University in Canada. The research was funded by the Wellcome Trust.
The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase. / Hawley, Simon A; Fullerton, Morgan D; Ross, Fiona A; Schertzer, Jonathan D; Chevtzoff, Cyrille; Walker, Katherine J; Peggie, Mark W; Zibrova, Darya; Green, Kevin A; Mustard, Kirsty J.; Kemp, Bruce E; Sakamoto, Kei; Steinberg, Gregory R; Hardie, D Grahame.In: Science, 2012.
Research output: Contribution to journal › Article