Dicyclohexylamine effects on HTC cell polyamine content and ornithine decarboxylase activity.
Dicyclohexylamine, a spermidine synthase inhibitor, was evaluated for its ability to alter specific polyamine levels in rat hepatoma HTC cells in culture. Media concentrations of 0.5 and 1.0 mM reduced the production of spermidine from putrescine and enhanced the conversion of existing spermidine to spermine. This created a very interesting change in polyamine levels such that after 24 h putrescine content was almost 3-times control values and spermine was about twice, while spermidine was lowered to about 10% of control cultures. This pattern of polyamines is quite distinct from that induced by the common polyamine biosynthetic inhibitors like methylglyoxal bis(guanylhydrazone) and difluoromethylornithine and replicates the pattern induced by S-adenosyl-1,8-diamino-3-thiooctane, a transition-state analog designed as a specific inhibitor of spermidine synthase. When cells were stimulated by serum addition, the presence of dicyclohexylamine caused an extraordinarily large induction in ornithine decarboxylase in spite of the abnormally high levels of both putrescine and spermine. The concomitant depression of spermidine levels induced a 4-fold increase in the stability of this enzyme that could be reversed by the addition of exogenous spermidine. The data suggest that spermidine induces, perhaps at the transcriptional level, a protein that is necessary for the characteristically very rapid inactivation of ornithine decarboxylase.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003514:Cyclohexylamines / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D008935:Mitoguazone / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D003514:Cyclohexylamines; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C011769:dicyclohexylamine; D013096:Spermine; D009955:Ornithine Decarboxylase; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine