Cytotoxicity of polyamines to Amoeba proteus: Role of polyamine oxidase |
| |
Authors: | E Schenkel J G Dubois M Helson-Cambier M Hanocq |
| |
Institution: | (1) Laboratory of Toxicology and Bioanalytical Chemistry, Université Libre de Bruxelles (ULB), Institute of Pharmacy, Brussels, Belgium;(2) Institute of Pharmacy, Laboratory of Toxicology and Bioanalytical Chemistry, Université Libre de Bruxelles (ULB), CP 205/1, Boulevard du Triomphe, 1050 Brussels, Belgium |
| |
Abstract: | It has been shown that oxidation of polyamines by polyamine oxidases can produce toxic compounds (H2O2, aldehydes, ammonia) and that the polyamine oxidase-polyamine system is implicated, in vitro, in the death of several parasites. Using Amoeba proteus as an in vitro model, we studied the cytotoxicity to these cells of spermine, spermidine, their acetyl derivatives, and their hypothetical precursors. Spermine and N
1-acetylspermine were more toxic than emetine, an amoebicidal reference drug. Spermine presented a short-term toxicity, but a 48-h contact time was necessary for the high toxicity of spermidine. The uptake by Amoeba cells of the different polyamines tested was demonstrated. On the other hand, a high polyamine oxidase activity was identified in Amoeba proteus crude extract. Spermine (theoretical 100%) and N
1-acetylspermine (64%) were the best substrates at pH 9.5, while spermidine, its acetyl derivatives, and putrescine were very poorly oxidized by this enzyme (3–20%). Spermine oxidase activity was inhibited by phenylhydrazine (nil) and isoniazid ( 50%). Mepacrine did not inhibit the enzyme activity at pH 8. Neither monoamine nor diamine oxidase activity ( 10%) was found. It must be emphasized that spermine, the best enzyme substrate, is the most toxic polyamine. This finding suggests that knowledge of polyamine oxidase specificity can be used to modulate the cytotoxicity of polyamine derivatives. Amoeba proteus was revealed as a simple model for investigation of the connection between cytotoxicity and enzyme activity.Abbreviations DAO
diamine oxidase
- DFMO
DL- -difluoromethylornithine
- DP
1-3-diaminopropane
- IC50
50% inhibition concentration
- MAO
monoamine oxidase
-
N
1-ACSP;
N
1-acetylspermine
- N1-ACSPD
N
1-acetylspermidine
-
N
8-ACSPD
N
8-acetylspermidine
- ODC
ornithine decarboxylase
- PAO(s)
polyamine oxidase(s)
- PUT
putrescine
- SP
spermine
- SPD
spermidine |
| |
Keywords: | Amoeba proteus cytotoxicity polyamine polyamine oxidase spermine |
本文献已被 SpringerLink 等数据库收录! |
|