A comparative study on proliferation, macromolecular synthesis and energy metabolism of in vitro-grown Ehrlich ascites tumor cells in the presence of glucosone, galactosone and methylglyoxal.
Proliferation of in vitro grown Ehrlich ascites tumor cells is completely inhibited by 0.2-0.4 mM methylglyoxal and 1-2 mM glucosone or galactosone without severely affecting viability (dye exclusion test); no phase-specific arrest of cell growth is observed. Incorporation of [14C] thymidine into the acid-insoluble fraction of the cells decreases within a few minutes to less than 50% of that in controls in the presence of 0.4 mM methylglyoxal, and 2 mM glucosone or galactosone causes a comparable inhibition of DNA synthesis after 2 h or 4 h, respectively. The action of 0.4 mM methylglyoxal inhibits incorporation of [14C] leucine within a few minutes by more than 70%, while 2 mM glucosone and galactosone are significantly less effective (50%-60% inhibition after 12 h). While methylglyoxal and galactosone do not severely affect lactate production of the cells, 2 mM glucosone reduces glycolysis by 60%-70%; ATP/ADP ratios did not fall below 3.5 in the presence of the inhibitors (controls 4-6). It is suggested that the reaction potentialities of the oxaldehyde function of the inhibitors play an important role in their growth-inhibitory activity, besides exerting a specific effect on hexokinase (glucosone) and UTP-trapping activity.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives* / Q000494:pharmacology; D007661:Ketoses / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011765:Pyruvaldehyde / Q000494:pharmacology*
D000447:Aldehydes; D004273:DNA, Neoplasm; D007661:Ketoses; D009363:Neoplasm Proteins; C017022:glucosone; C035750:galactosone; D000244:Adenosine Diphosphate; D011765:Pyruvaldehyde; D000255:Adenosine Triphosphate; D005690:Galactose