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Dicyclohexylamine, a potent inhibitor of spermidine synthase in mammalian cells
Author(s) -
Hibasami H.,
Tanaka M.,
Nagai J.,
Ikeda T.
Publication year - 1980
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(80)80537-0
Subject(s) - spermidine , medicine , biochemistry , chemistry , enzyme
Much effort has been made to develop specific inhibitors of polyamine synthesis which may help in elucidating the role of polyamines in cellular metabolism and in cell proliferation in particular [l-7]. Furthermore, inhibitors of polyamine synthesis may find applications as antiproliferative agents. Four enzymes are involved in the synthesis of polyamines in eukaryotic cells, i.e., ornithine decarboxylase, S-adenosylmethionine(SAM) decarboxylase and two aminopropyltransferases, one catalyzing the synthesis of spermidine, the other producing spermine [8-121. Most inhibitory used are inhibitors of the two decarboxylases, whereas several inhibitors are reported at the aminopropyltransferases [ 13-151. The relative activities of these enzymes must determine which of the polyamines accumulate in the cells. Marked differences in the spermidine to spermine ratio have been observed in comparisons of various mammalian cells [8,16] and spermidine levels are usually elevated in response to growth-promoting stimuli [8,16,17]. Here we demonstrate that partially purified spermidine synthase from rat ventral prostate was strongly inhibited by dicyclohexylamine and also by cyclohexylamine, and that administration of dicyclohexylamine caused a decrease in the concentration of spermidine but not spermine in the liver of partially hepatectomized rats. These inhibitors may be useful as experimental tools for elucidating the physiological function of the polyamines.