Energy metabolism of adriamycin-sensitive and -resistant Ehrlich ascites tumor cells.
Respiration, glycolysis, utilization of carbon from 14C-labeled glucose and the activities of some regulatory enzymes of the Krebs cycle and glycolysis in adriamycin-sensitive (EH-WT) and -resistant (EH-ADR) Ehrlich ascites tumor cells have been investigated. The following summarizes the results: 1. Compared with wild-type cells, EH-ADR cells exhibited an enhanced rate of oxygen consumption as well as of ATP production (2-fold). 2. When the cells were supplied with glucose as the only added energy source, the aerobic lactate production was 30% higher in EH-ADR cells. However, in spite of the enhanced glycolysis, 50% of total cell ATP was still supplied by oxidative phosphorylation, whereas in EH-WT cells 65% of ATP was derived from glycolysis. 3. The activities of the regulatory enzymes were remarkably more elevated in EH-ADR cells. 4. The amount of glucose carbon atoms metabolized through the Krebs cycle and pentose phosphate pathway in EH-ADR cells was significantly higher than in EH-WT cells. 5. These differences confirmed a modified energy metabolism in resistant cells and reflected metabolic adaptations associated with the development of multidrug resistance.
Miccadei
S
S
Laboratory for Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Fanciulli
M
M
Bruno
T
T
Paggi
M G
MG
Floridi
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D004317:Doxorubicin / Q000032:analysis / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D005947:Glucose