Hypoxically cultured cells of oral squamous cell carcinoma increased their glucose metabolic activity under normoxic conditions

Abstract

Objective The oxygen concentration within cancer tissue is known to be low, but is expected to increase rapidly when oxygen is supplied by angiogenesis and hematogenous metastasis, suggesting that rapid increases in oxygen levels might influence cancer cell physiology. Therefore, we investigated the effects of oxygen concentration fluctuations on the glucose metabolism of cancer cells. Methods The glucose metabolism of oral squamous cell carcinoma (HSC-2 and HSC-3) and normal epithelial (HaCaT) cells cultured under normoxic (21% oxygen) or hypoxic (1% oxygen) conditions was measured using a pH-stat system under normoxic or hypoxic conditions. The acidic end-products and reactive oxygen species (ROS) generated by glucose metabolism were also measured. Results Under normoxic conditions, the metabolic activity of hypoxically cultured cancer cells was significantly increased, and the production of acids other than lactate was upregulated, while the normal cells did not respond to rapid increases in oxygen levels. ROS production was higher in normoxic conditions in all cells, especially the hypoxically cultured HSC-3 cells. Conclusions Rapid increases in oxygen levels might enhance the glucose metabolism of hypoxically cultured cancer cells by mainly activating the TCA cycle and electron transport system, which might activate cancer cells through the ATP and ROS generation.