Emetine Inhibits Glycolysis in Isolated, Perfused Rat Hearts

Abstract

This work was designed to test whether phosphofructokinase is a target for emetine action on the heart. The effects of 37 microM emetine on the activities of phosphofructokinase and hexokinase were measured in homogenates from perfused hearts. The action of increasing concentrations of emetine was determined in nonperfused heart homogenates. The effect of 37 microM emetine or control solutions on the concentration of fructose-6-phosphate and fructose- 1,6-phosphate was measured. The effect of 37 microM emetine or control perfusion on the utilization of fructose-6-phosphate by phosphofructokinase in centrifugation supernatants of homogenates and in reconstituted 27,000g pellets was measured. Double-reciprocal plots of fructose-6-phosphate concentrations vs phosphofructokinase activities were plotted. Emetine decreased phosphofructokinase activity in homogenates from both perfused and nonperfused hearts. Emetine did not inhibit cardiac hexokinase activity. In homogenates from nonperfused hearts, the maximal inhibition with high concentrations of emetine was approx 50%. Emetine perfusion caused a simultaneous increase in the phosphofructokinase substrate fructose-6-phosphate and a decrease in the phosphofructokinase product fructose-1,6-bisphosphate. Phosphofructokinase and, consequently, glycolytic flux appear to be subcellular targets for emetine in the heart. Homogenate centrifugation studies indicate that emetine acts on bound rather than unbound phosphofructokinase. The inhibition may be uncompetitive in nature.

Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells

“…Emetine causes concern regarding its significant toxicity, particularly the muscle weakness and cardiotoxicity associated with its chronic use [16,24,25,26,27,28,29]. To prevent these possible adverse effects, which might impede its clinical use, we tested whether low-dose emetine also performed well in combination with cisplatin.…”

Biological Activities of Emetine

“…For instance, chronic usage has been reported to result in myopathy [74]. In addition, cardiotoxicity, including cardiomyopathy, is associated with chronic use of emetine [74][75][76]. In a study relating protein pharmacology to ligand chemistry, new targets were discovered for emetine and these were linked to some of the side effects of its pharmacological use [77].…”