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 Grahame 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 this week 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.
He added: “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.”
By acting on targets other than AMPK, aspirin acts as a painkiller, reduces fever, and has anti-inflammatory effects. Its effects on platelets mean it is also used to prevent formation of blood clots that might lead to heart attacks and strokes. Studies of people taking aspirin long-term have shown that they have a lower incidence of cancer.
Professor Hardie continued, “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.
He added: “Despite its anticancer 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 anticancer effects are mediated by AMPK, then other salicylate-based drugs, with fewer side effects than aspirin, might perhaps be used instead.”