Antileukemic effects of non-metabolizable derivatives of spermidine and spermine.
To determine whether non-metabolizable derivatives of spermidine and spermine exert anticancer effects, L1210 leukemic mice were treated with 5,8-dimethylspermidine and 5,8-dimethylspermine. Both derivatives cured 5% of the leukemic mice. The increase in median survival time, however, was slight. In combination with alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, only 5,8-dimethylspermine had a favorable effect. Treatment with DFMO is known to increase the uptake of extracellular polyamines and presumably their derivatives, by depleting the intracellular putrescine and spermidine content. However, treatment of L1210 leukemia cells in vitro with DFMO did not affect the uptake of the methyl-substituted polyamines added to the growth medium. 5,8-Dimethylspermidine and 5,8-dimethylspermine repressed the ornithine decarboxylase activity when added to cultures of L1210 leukemia cells. S-Adenosylmethionine decarboxylase activity was only repressed by 5,8-dimethylspermine. This finding may explain the potentiation by this derivative and not by 5,8-dimethylspermidine, of the antileukemic effect of DFMO.
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Department of Oncology, University of Lund, Sweden.
Persson
L
L
Seiler
N
N
Heby
O
O
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009955:Ornithine Decarboxylase / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
C057952:5,8-dimethylspermine; C081041:5,8-dimethylspermidine; D013096:Spermine; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D013095:Spermidine; D000518:Eflornithine