Since cancer cells produce large amounts of lactate via aerobic glycolysis and since an acidic pH has been shown to selectively enhance the cytotoxic effects of hyperthermia, we are examining the influence of cell exposure to drugs which inhibit lactate transport and lower intracellular pH upon cytotoxic effects of hyperthermia. Quercetin, a bioflavonoid that produces lactate transport inhibition, was not cytotoxic up to 4 hr at 37° (0.1 mm). When HeLa cells were exposed to quercetin at 41 and 42°, significant potentiation of hyperthermia-induced cytotoxicity was observed. The magnitude of the potentiation was dependent on the drug concentration, pH of the culture medium, temperature, and duration of treatment. In contrast, treatment of cells with rutin, a structurally related bioflavonoid that lacks the property of lactate transport inhibition, showed no hyperthermic potentiation.
Supported in part by National Cancer Institute Grant CA-33894.