Cytostatic activity and metabolic effect of N-trichloromethylthio-4-cyclohexane-1,2-dicarboximide on Ehrlich ascites carcinoma cells.

Effect of N-trichloromethylthio-4-cyclohexane-1,2-dicarboximide (NTCD) on energy-yielding and energy-requiring processes in Ehrlich ascites carcinoma (EAC) cells have been investigated. At concentrations higher than 10 micrograms/ml NTCD causes a rapid and practically full inhibition of both aerobic glucose uptake and lactate formation. On the other hand, at concentrations lower than 10 micrograms/ml, these metabolic parameters are stimulated. The stimulation of glycolysis, according to our previous results, suggests the interference of NTCD with mitochondrial functions. This image is supported by the marked inhibitory effect on NTCD on respiration of isolated mitochondria. The inhibition of glycolysis with higher concentrations of NTCD is the consequence of inactivation of hexokinase (EC 2.7.1.1), eventually of 6-phosphofructokinase (FC 2.7.1.11). The described effects of NTCD are given into coherence with chemical modification of appropriate functional SH groups of EAC cells by the compound studied. Proportionally to the dose and time NTCD inhibits the synthesis of macromolecules in whole EAC cells as measured by the incorporation of labeled adenine and valine into the TCA-insoluble fractions. The inhibition of biosynthetic processes followed is the consequence of exclusion of key processes in the energy metabolism and leads to the loss of EAC cells transplantability.