Inhibition of lactate transport and glycolysis in Ehrlich ascites tumor cells by bioflavonoids

Abstract

Bioflavonoids are potent inhibitors of lactate transport in [mouse] Ehrlich ascites tumor cells. The most effective bioflavonoids have 4-5 hydroxyl groups. Sugar substitution at carbon 3, or reduction of the double bond between carbons 2 and 3, decreases their inhibitory activity. Quercetin, the most extensively studied of these compounds, inhibits lactate efflux by 50% at 0.1 .mu.g/mg of protein. On addition of quercetin to glycolyzing Ehrlich ascites tumor cells, lactate accumulates inside the cell and the intracellular pH drops. Total lactate production is also inhibited. Nigericin prevents the internal acidification that occurs in the presence of quercetin and also reduces the inhibition of glycolysis. Inhibition of lactate efflux apparently can affect glycolysis through a lowering of the intracellular pH. The inhibitory effect of quercetin on glycolysis can be explained by its effect on lactate efflux and its previously reported effect on the Na+-K+ ATPase.