In vivo growth inhibition of L1210 leukemia by 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), a new inhibitor of S-adenosylmethionine decarboxylase.
We studied the in vivo growth-inhibitory effect of the new S-adenosylmethionine decarboxylase inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A). L1210-bearing DBA-2 mice were treated with increasing CGP 48664A doses from 1 day after i.p. L1210 cell inoculation. Treatment was continued for 4 days, after which all mice were killed. CGP 48664A caused dose-related exponential decreases of L1210 cell numbers and spermidine and spermine contents. Putrescine contents increased exponentially. Polyamine changes in spleen and liver were less profound. L1210 growth inhibition was not accompanied by changes in cell cycle phase distribution. It is concluded that CGP 48664A is an effective inhibitor of S-adenosylmethionine decarboxylase but that CGP 48664A-induced changes in intracellular polyamine compositions are not necessarily the cause of growth inhibition.
Dorhout
B
B
Central Laboratory for Clinical Chemistry, University Hospital Groningen, The Netherlands.
Te Velde
R J
RJ
Ferwerda
H
H
Kingma
A W
AW
De Hoog
E
E
Muskiet
F A
FA
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007189:Indans / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000378:metabolism
D000578:Amidines; D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D007189:Indans; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; D012437:Adenosylmethionine Decarboxylase