Dynamic analysis of metabolic effects of chloroacetaldehyde and cytochalasin B on tumor cells using bioelectronic sensor chips.
PURPOSE: To study the interplay of drugs and energy metabolism of tumor cells, metabolic changes induced by chloroacetaldehyde and cytochalasin B were analyzed in colon carcinoma cells LS174T. METHODS: O(2)-consumption and extracellular acidification were recorded using a bioelectronic sensor-chip system, which monitors these parameters in a culture continuously for at least 24 h. In parallel cultures cell number, cellular ATP-content, mitochondrial transmembrane potential, and the content of reactive oxygen species (ROS) were determined. RESULTS: When cell death was induced by chloroacetaldehyde (50 muM), the rate of acidification declined gradually for the next 15 h, while O(2)-consumption decreased rapidly within 30 min. This correlated with a loss in mitochondrial potential. However, cellular ATP-level showed a transient increase at 2 h; also ROS levels increased up to 6 h. In cells treated with cytochalasin B (2 muM), which inhibits glucose uptake, the rate of O(2)-consumption increased and the acidification activity dropped, even upon glutamine depletion. Mitochondrial membrane potential transiently increased after 1 h, while ATP-content decreased; there was no change in the level of ROS. CONCLUSION: The pattern of changes in basic energy metabolism differs with the type of cell death and growth inhibition involved in the cytotoxic action of two different drugs.