Another Aspirin Connection

The story of aspirin just got a new wrinkle. Scientists report that high doses of salicylate, which is both a breakdown product of aspirin and the pain-relieving willow bark component that spurred aspirin’s development, activate the energy sensor adenosine mono­phosphate-activated protein kinase, or AMPK (Science, DOI: 10.1126/science.1215327). Aspirin and salicylate block pain-mediating cyclooxygenase enzymes, but research in mice suggests those enzymes don’t underlie all the drugs’ effects. In cells and in mice, D. Grahame Hardie of Scotland’s University of Dundee and coworkers learned, salicylate behaves like A-769662, a synthetic allosteric activator of AMPK that influences how animals use fat as an energy source. Aspirin has anticancer benefits, and the team thinks AMPK might be behind them, because metformin, an AMPK activator and diabetes drug, also protects against cancer. “This is an interesting and surprising story that links salicylate and AMPK activity,” says Jay H. Chung, an AMPK expert at the National Institutes of Health. “However, I don’t think this study is applicable to aspirin’s cancer prevention benefits in the real world,” he adds, because someone would have to consume a ballpark 10 to 20 adult aspirins at once, a borderline toxic level, to activate AMPK.