The relationship between cell proliferation and the rates of glycolysis and oxidative phosphorylation in HeLa (human) and AS-30D (rodent)
tumor cells was evaluated. In
glutamine plus
glucose medium, both
tumor lines grew optimally. Mitochondria were the predominant source of
ATP in both cell types (66-75%), despite an active glycolysis. In
glucose-free medium with
glutamine, proliferation of both lines diminished by 30% but oxidative phosphorylation and the cytosolic
ATP level increased by 50%. In
glutamine-free medium with
glucose, proliferation, oxidative phosphorylation and
ATP concentration diminished drastically, although the cells were viable.
Oligomycin, in medium with
glutamine plus
glucose, abolished growth of both
tumor lines, indicating an essential role of mitochondrial
ATP for
tumor progression. The presumed mitochondrial inhibitors
rhodamines 123 and 6G, and
casiopeina II-gly, inhibited
tumor cell proliferation and oxidative phosphorylation, but also glycolysis. In contrast,
gossypol, iodoacetate and
arsenite strongly blocked glycolysis; however, they did not affect
tumor proliferation or mitochondrial metabolism. Growth of both
tumor lines was highly sensitive to
rhodamines and
casiopeina II-gly, with IC(50) values for HeLa cells lower than 0.5 microM, whereas viability and proliferation of human lymphocytes were not affected by these drugs (IC(50) > 30 microM). Moreover,
rhodamine 6G and
casiopeina II-gly, at micromolar doses, prolonged the survival of animals bearing i.p. implanted AS-30D
hepatoma. It is concluded that fast-growing
tumor cells have a predominantly oxidative type of metabolism, which might be a potential therapeutic target.