EFFECT OF THE ANTITUMOR DRUG LONIDAMINE ON GLUCOSE-METABOLISM OF ADRIAMYCIN-SENSITIVE AND ADRIAMYCIN-RESISTANT HUMAN BREAST-CANCER CELLS

The effect of lonidamine on glucose metabolism, hexokinase activity an d adenylate pool of MCF-7 human breast cancer cells sensitive and resi stant to adriamycin has been investigated. The following summarizes th e results: 1. In both cell types the greatest part of glucose was meta bolized to lactate, whereas only a small proportion of glucose carbon atoms was incorporated into CO2, lipids, nucleic acids, and supporting structures. 2. Glucose utilization, lactate production, and ATP conte nt were higher in resistant cells due to a greater activity of mitocho ndrial hexokinase. 3. Lonidamine decreased glucose utilization, aerobi c glycolysis and ATP content in both cell types and the effect was sig nificantly higher on resistant cells. 4. The extent of inhibition in s ensitive and resistant cells overlapped that found for mitochondrially bound hexokinase, thus indicating that the greater sensitivity of res istant cells to lonidamine was due to their higher amount of bound hex okinase. These findings confirmed a modified glucose metabolism in cel ls with resistant phenotype and suggested that lonidamine might be use fully used to reduce or overcome multidrug resistance of those cells w ith a reduced ability to accumulate and retain antitumor drugs.