Drug Screening for Glycolysis Pathway in Living Cancer Cells Using ¹⁹F NMR

Glycolysis is a fundamental process for the generation of cellular energy, and its dysregulation has been linked to a number of diseases, including obesity, neurological disorders, and cancer. Targeting glycolysis is therefore a promising therapeutic strategy. However, effective drugs that specifically target glycolysis are still lacking. In this study, we introduce a novel approach utilizing ¹⁹F NMR to monitor early glycolysis in living MCF-7 cells. By tracking metabolites downstream of the glucose analogue 2-fluoro-2-deoxyglucose (2-FDG), we successfully observed the activity of key glycolytic components, such as glucose transporters (GLUTs) and hexokinase (HKs). Our results reveal distinct metabolic profiles upon inhibition of these targets, advancing the understanding of glycolytic regulation. In addition, we applied this approach to screen traditional Chinese medicines for their effects on glycolysis and identified <i>Salvia miltiorrhiza</i> and <i>Fructus evodiae</i> as modulators with contrasting effects on glycolytic metabolism. This dual modulation highlights their potential as valuable tools for therapeutic intervention. Our study provides an innovative methodology for both the exploration of glycolytic pathways and the discovery of novel therapeutics, offering new perspectives for drug development targeting metabolic diseases.