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Published on: June 9, 2019
Drug Screening for Glycolysis Pathway in Living Cancer Cells Using 19F NMR
Biao Liu1, Tao Huang1, Xiong Xiao1,2
1Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement of Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China.
Abstract:
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 Salvia miltiorrhiza and Fructus evodiae 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.
Insights
This study introduces a novel 19F NMR method to track early glycolysis in living cells. It identifies Salvia miltiorrhiza and Fructus evodiae as potential drug candidates targeting cellular energy metabolism.
Area of Science:
- Biochemistry
- Cellular Metabolism
- Medical Science
Background:
- Glycolysis is crucial for cellular energy production.
- Dysregulated glycolysis is implicated in diseases like cancer and obesity.
- Targeting glycolysis offers therapeutic potential, but specific drugs are limited.
Purpose of the Study:
- To develop a novel 19F NMR approach for monitoring early glycolysis in living cells.
- To investigate the effects of inhibiting key glycolytic enzymes.
- To screen traditional Chinese medicines for glycolytic modulation.
Main Methods:
- Utilized 19F NMR spectroscopy to track metabolites downstream of 2-fluoro-2-deoxyglucose (2-FDG).
- Monitored the activity of glucose transporters (GLUTs) and hexokinase (HKs).
- Applied the method to screen traditional Chinese medicines, including Salvia miltiorrhiza and Fructus evodiae.
Main Results:
- Successfully observed early glycolytic activity in MCF-7 cells.
- Revealed distinct metabolic profiles upon inhibition of GLUTs and HKs.
- Identified Salvia miltiorrhiza and Fructus evodiae as modulators of glycolytic metabolism with contrasting effects.
Conclusions:
- The 19F NMR approach provides an innovative methodology for studying glycolytic pathways.
- This method facilitates the discovery of novel therapeutics targeting metabolic diseases.
- Salvia miltiorrhiza and Fructus evodiae show potential for therapeutic intervention in metabolic disorders.
