Approved Drugs that Shift Cellular Energy Metabolism toward Glycolysis Identified

This article discusses the discovery of several drugs that affect cellular energy metabolism in animals. Changes in energy production pathways in cells can occur naturally, such as in development or in response to energetically demanding activities, but can also occur due to disease. The goal of the team that discovered these drugs was to identify compounds that can induce this shift in a safe manner, and research how the therapeutic value of this shift. Cancer cells produce energy predominantly through glycolysis, so a mechanism that would switch energy production from this may suppress tumor growth.

Previous studies show that mitochondrial respiration could mimic ischemic preconditioning. This is when there is a brief decrease in blood supply to a tissue, which can protect it from future damage if blood supplies are completely cut off. A new screening strategy was created by the team, in which there were two environments: one that had glucose (glycolysis and respiration), and another that had galactose (respiration). A drug that would be able to redirect metabolism from respiration to glycolysis would would stop the growth of cells in the galactose while it would have minimal effect on the cells in the glucose. Several drugs were identified to cause a shift in energy metabolism, including anticancer drugs that inhibit rapidly proliferating cell growth.

Most drugs that mimic ischemic preconditioning are too toxic for human cells, but the researchers were able to identify eight drugs that produced a less intense, but significant, shift from respiration to glycolysis. One of these drugs was meclizine, which is an over-the-counter drug that is used for treating nausea and vertigo. This drug was tested on and it was discovered that pretreatment with meclizine reduced ischemic damage in cardiac cell in the case of a heart attack. It also reduced damage to brain cells when tested on a stroke model. A lot of testing is still needed before this type of drug can be used on human cases.

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