Scopoletin and Morin Inhibit Lactate Dehydrogenase Enzyme Activity, Which Is Critical for Cancer Metabolism

Abstract

Background: Lactate dehydrogenase (LDH) is a tetrameric enzyme that catalyzes the interconversion of pyruvate to L-lactate. The importance of this enzyme is because LDH isoenzymes are involved in cancer, heart, and liver diseases. Inhibition of this enzyme can help prevent and treat different diseases. Morin is a flavonoid found in the Moraceae family and scopoletin is a coumarin found in Scopolia genus. Objectives: The aim of this study was to determine the effect of morin and scopoletin as two natural products on the activity and structure of lactate dehydrogenase enzyme. Methods: Morin and scopoletin were examined for inhibition of the activity of LDH in 100 mM sodium phosphate buffer pH 7.5, at room temperature using UV-V spectrophotometry. Fluorescence spectroscopy was used to characterize protein structural changes in the presence of morin and scopoletin. Results: Km and Vmax of LDH for pyruvate were 11.69 mM and 1.258 mM/min, respectively. The kinetic results showed that morin and scopoletin are LDH inhibitors. The Ki values of morin and scopoletin were determined as 1.78 µM and 0.8 µM, respectively, using a secondary plot. Fluorescence intensity quenching and red shift of the maximum wavelength of emission in a concentrationdependent manner showed that morin and scopoletin bind to LDH and affect its structure. Conclusions: The results suggest that morin and scopoletin bind to LDH, influence its conformation and inhibit its activity. Scopoletin showed more effective inhibition of LDH activity and it can be a promising candidate in the field of tumor metabolism inhibitors.