The long-lasting antiproliferative effect of 15-deoxyspergualin through its spermidine moiety

Citation
M. Kawada et al., The long-lasting antiproliferative effect of 15-deoxyspergualin through its spermidine moiety, J ANTIBIOT, 53(7), 2000, pp. 705-710
Citations number
16
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF ANTIBIOTICS
ISSN journal
00218820 → ACNP
Volume
53
Issue
7
Year of publication
2000
Pages
705 - 710
Database
ISI
SICI code
0021-8820(200007)53:7<705:TLAEO1>2.0.ZU;2-D
Abstract
15-Deoxyspergualin (DSG) inhibited growth of mouse EL-4 lymphoma cells with an IC50 0.02 mu g/ml. Even though the cells were treated with DSG for only 4 hours and then washed, the antiproliferative effect lasted long with an IC50 0.4 mu g/ml. DSG has spermidine and guanidine moieties in its structur e. One decomposed element containing guanidine moiety inhibited the growth at higher doses than DSG, but the effect did not last long unlike DSG. Whil e another element containing spermidine moiety did not affect the growth, i t diminished the long-lasting antiproliferative effect of DSG by pretreatme nt of the cells. Pretreatment with polyamines such as putrescine, spermidin e, and spermine also diminished the effect of DSG. Furthermore, N-alkylatio n of spermidine moiety in DSG abolished the antiproliferative effect. These results suggested that DSG binds to the cells through its spermidine moiet y and exerts its long-lasting antiproliferative effect.