EFFECT OF LONIDAMINE ON THE ENERGY-METABOLISM OF EHRLICH ASCITES TUMOR-CELLS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (11) , 4661-4666
Abstract
The action of Lonidamine [1-(2,4-dichlorobenzyl)-1-H-indazol-3-carboxylic acid] on oxygen consumption and the rate of aerobic and anaerobic lactate production by Ehrlich [mouse] ascites tumor cells was investigated. The rate of oxygen consumption decreases exponentially with the increase of Lonidamine concentration, with maximal inhibition occurring at 0.40 mM Lonidamine. The rate of aerobic lactate production is inhibited to the same extent as is the oxygen consumption. The maximum effect is observed at 0.12 mM Lonidamine and the decrease is linear with Lonidamine concentration. Anaerobic lactate production is more sensitive to Lonidamine and complete inhibition can be observed by raising the concentration to 0.6 mM. The possibility that the decrease observed in lactate production was secondary to the inhibition of Na- and K-containing ATP was excluded because the drug has no effect on this enzyme. Mitochondrial ATPase was not affected. Lonidamine however, inhibited the activity of mitochondrially-bound hexokinase to approximately the same extent as it inhibited aerobic glycolysis (.apprx. 70%). Inhibition of the glycolysis of Ehrlich ascites tumor cells by Lonidamine results from an effect of the drug on the mitochondrially-bound hexokinase.