Proliferation, macromolecular synthesis and energy metabolism of in vitro grown Ehrlich ascites tumor cells after inhibition of ATP-ADP translocation by atractyloside.
In the presence of 3 mM atractyloside, growth of in vitro cultured Ehrlich ascites tumor cells is inhibited by 70% within 24 h. Viability of the cells is not severely affected (dye exclusion test). Incorporation of 2-[14C]-thymidine and U-[14C]-leucine into acid insoluble precipitate were reduced by 80% or 20% respectively as compared to controls. Flow cytometric analysis of cell cycle progression revealed a retardation rather than an arrest of cell growth by atractyloside. Morphological changes of the cells primarily concern mitochondria which are spherical shaped with translucent matrix rid of cristae. After transfer of atractyloside treated cells to normal medium, proliferation and macromolecular synthesis normalized within 3 to 6 h. At 3 mM of atractyloside, glucose consumption of the cells increased by 25%, lactate production by 30%. Lactate/glucose ratio was 1.9 after 24 h. Oxygen uptake was reduced by 35% after 12 h. The [ATP]/[ADP] ratio of the whole cells runs through a maximum between 12 and 18 h. The ratio never falls below 5.0. The ATP/ADP concentration ratio in the mitochondrial and extramitochondrial compartment were increased as compared to controls. delta G of ATP hydrolysis of the intact cells was in a normal range (-50 kJ), energy charge was 0.86 (controls 0.88). Transport of amino acids, uptake of glucose and activity of Na+, K+-ATPase of the plasma membrane were not impaired by 3 mM atractyloside.(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001278:Atractyloside / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008854:Microscopy, Electron; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010710:Phosphates / Q000032:analysis
D006027:Glycosides; D010710:Phosphates; D001278:Atractyloside; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D009713:Nucleotidyltransferases; D009955:Ornithine Decarboxylase