Dynamic analysis of metabolic effects of chloroacetaldehyde and cytochalasin B on tumor cells using bioelectronic sensor chips.
OBJECTIVE
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.


CONCLUSIONS
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.
Motrescu
E R
ER
Heinz-Nixdorf-Chair for Medical Electronics, Technical University of Munich, Germany.
Otto
A M
AM
Brischwein
M
M
Zahler
S
S
Wolf
B
B
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism*; D015374:Biosensing Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D003571:Cytochalasin B; C004656:chloroacetaldehyde; D000079:Acetaldehyde