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The Effect of Flavonoids on Aerobic Glycolysis and Growth of Tumor Cells¹

Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853

Certain bioflavonoids inhibit the glycolysis of a variety of tumor cells by interfering with the generation of adenosine diphosphate and inorganic phosphate which are required for glycolysis. Tetra- and pentahydroxy flavones with hydroxyl groups at 3, 3', 4', 5, and 7 (e.g., quercetin) are the most active. They inhibit the activity of isolated Na⁺-K⁺-adenosinetriphosphatase of the plasma membrane and of mitochondrial adenosinetriphosphatase, but under appropriate conditions do not interfere with the ion transport activity of the adenosinetriphosphatases. Therefore, they increase the translocation efficiency of the ion pump. It was shown that in several tumor cells loosely coupled ion pumps are responsible for the high rate of aerobic glycolysis. In such cells addition of quercetin induces the cells to pump ions with greater efficiency.

In attempts to elucidate the role of the high aerobic glycolysis, the effect of quercetin on the growth of several cell lines was examined. Since bicarbonate and serum albumin were found to counteract the effect of quercetin, the cells were grown in tissue cultures at low concentrations of these compounds. Pronounced inhibition of growth was observed at 5 to 20 µg of quercetin per ml of growth medium.

¹ This investigation was supported by Grants CA-08964 and CA-14454 from the National Cancer Institute and Grant BC-156 from the American Cancer Society.

Received 1/23/75. Accepted 4/ 7/75.

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