Toxicity and effects of epidermal growth factor on glucose metabolism of MDA-468 human breast cancer cells.
Epidermal growth factor (EGF) has an in vitro inhibitory effect on tumor cells which exhibit a high number of EGF receptors (EGFR). Studies were performed in order to delineate the effects of EGF on glucose metabolism of MDA-468 human breast cancer cells, which have a large number of EGFR. Glucose consumption and lactate production were found to be substantially increased in MDA-468 cells following EGF exposure, while no such effects were detected in MCF-7 breast cancer cells, which have a very low number of EGFR. When glucose levels in the growth medium were increased, the toxicity of EGF was diminished. The energetic status of MDA-468 cells perfused with growth medium containing EGF was monitored by 31P magnetic resonance spectroscopy, and no signs of compromised metabolic state or viability were noted for up to 36 h. The rate of glucose transport and phosphorylation was quantitated by 13C magnetic resonance spectroscopy, utilizing [6-13C]2-deoxyglucose, and a 97% increase was found in MDA-468 cells following EGF administration. The profound effects of EGF on glucose metabolism in cells with very high numbers of EGFR and the lack of toxicity in the perfused system may indicate that the growth-inhibitory effect is confined to the in vitro cultured cells.
Kaplan
O
O
Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Jaroszewski
J W
JW
Faustino
P J
PJ
Zugmaier
G
G
Ennis
B W
BW
Lippman
M
M
Cohen
J S
JS
D001693:Biological Transport, Active / Q000187:drug effects; D001943:Breast Neoplasms; D002247:Carbon Isotopes; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D002247:Carbon Isotopes; D004815:Epidermal Growth Factor; D003847:Deoxyglucose; D005947:Glucose