The role of glycolysis in the growth of tumor cells. I. Effects of oxamic acid on the metabolism of Ehrlich ascites tumor cells in vitro.

It is now well known that tumor tissues, either in the form of solid tumors or as ascites cells, have a high rate of aerobic and anaerobic glycolysis. A theory on the origin of the tumor cell as proposed by Warburg (1,2) states that a normal cell becomes malignant as the result of impairment to its respiratory processes. Warburg has stated (1, 2) that in order for these cells to survive they must derive the energy that was once provided by respiration from other metabolic processes. Thus, he proposes that the increased rate of glycolysis in the tumor cell serves to provide energy for its survival. However, it has never been shown experimentally that tumor cells are dependent on glycolysis for survival. In the experiments to be reported, we have sought to establish conditions in which the glycolysis of tumor cells is specifically inhibited, whereas the respiration of the cells remains unaffected. These experiments were based on the view that glycolysis can be inhibited specifically only by inhibition of lactic dehydrogenase, since the latter is the only enzyme of the Embden-Meyerhof pathway of glycolysis which plays no role in the oxidat,ion of carbohydrate via pyruvic acid. Schwert et al. (3-6) have shown that, of a series of compounds structurally related to pyruvic acid, oxamic acid (H2N.CO. COOH) is the most potent competitive inhibitor of crystalline beef heart lactic dehydrogenase. The present experiments were designed to test whether oxamic acid could also inhibit lactic dehydrogenase in the intact Ehrlich ascites tumor cell and whether it is a specific inhibitor of this enzyme in the intact cell. The effect of the inhibition of lactic dehydrogenase on anaerobic glycolysis, aerobic glycolysis, oxygen uptake, and the Crabtree effect is reported below. A preliminary account of this work has appeared (7). Other studies of oxamate effects on glycolysis have also appeared (8, 9).