1984/08/01 by Pierre S. Mamont, Pierre S. MAMONT, M Siat +6 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Adenosylmethionine decarboxylase #Amino Acid Enzymes and Metabolism #Amino acid #Biochemistry #Biology #Cannabis and Cannabinoid Research #Cell culture #Cell growth #Chemistry #Enzyme #In vitro #Intracellular #Molecular biology #Ornithine #Ornithine decarboxylase #Ornithine decarboxylase antizyme #Polyamine #Polyamine Metabolism and Applications #Putrescine #Spermidine #Spermine
paper · pdf · doi:10.1111/j.1432-1033.1984.tb08308.x
openalex publication_date 1984/08/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/06/11
DL-alpha-Difluoromethylornithine (F2MeOrn), the most widely-used inhibitor of L-ornithine decarboxylase, has been a useful tool to demonstrate that polyamine biosynthesis is required to maintain maximum rates of cell proliferation. However, in most eukaryotic cell systems, F2MeOrn exerts cytostatic rather than cytotoxic effects. This may be due to the fact that this inhibitor creates only incomplete polyamine deficiency. In particular, F2MeOrn scarcely depletes intracellular spermine levels. We now demonstrate in rat hepatoma tissue culture (HTC) cells that (2R, 5R)-6-heptyne-2,5-diamine, a more potent irreversible inhibitor of L-ornithine decarboxylase than F2MeOrn, decreases the concentrations of all polyamines including spermine. In parallel with the depletion of these amines, there is a progressive decrease in the rate of cell proliferation and in cell viability. Restoration of the intracellular polyamine content, by addition to the medium of polyamines or a high concentration of L-ornithine, the substrate of L-ornithine decarboxylase, further demonstrates that the antiproliferative effects of (2R, 5R)-6-heptyne-2,5-diamine do result from polyamine deficiency. These findings support the concept that polyamines play an essential function in the cell division processes and emphasize the vital function of spermine in mammalian cells.