ISSN:
1573-6822
Keywords:
bisbenzylpolyamine analogs
;
cytotoxicity
;
DFMO
;
MDL 72,527
;
polyamine content
;
polyamine oxidase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract The effects of a series of bisbenzyldiamine analogs have been tested on P388D1 cell line in vitro. Their effects on cell growth, polyamine oxidase (PAO) activity and intracellular polyamine content were determined. The cytotoxicity tests were performed in culture medium supplemented with 100 μmol/L aminoguanidine (I), 100 μmol/L aminoguanidine and 100 μmol/L N,N′-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72,527) (II), and finally 100 μmol/L aminoguanidine and 200 μmol/L D,L-difluoromethylornithine (DFMO) (III). The IC50 values under conditions I and III were similar, suggesting that inhibition of ornithine decarboxylase by DFMO did not affect the biological effect of our derivatives. Spermine and spermidine remained nontoxic in conditions I and III. However in the condition II, the toxicity of all tested compounds (excepted spermidine) was increased, suggesting that the inhibition of cellular PAO increased their toxicity. The enzymatic test of PAO showed that at high doses inhibition of this enzyme by putrescine analogs occurred, while the N-methylated propanediamine derivative increased the enzyme activity; however, these results do not correlate with cytotoxicity tests. When these derivatives were incubated for 48 h with the cells, all of them increased the cell content in putrescine (∼160%) and spermine (∼145%) and decreased the spermidine content (∼75%) without any modification of the total amount of polyamine. The correlation between the cytotoxic results and the intracellular polyamine determination shows that the increase in spermine content along with the inhibition of retroconverting PAO enzyme increases the toxic effect of tested compounds (including spermine), suggesting that spermine toxicity is more important in the absence of intracellular oxidation processes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007503928993
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