Inhibition of polyamine oxidase enhances the cytotoxicity of polyamine oxidase substrates. A model study with N-1-(n-octanesulfonyl)spermine and human colon cancer cells
N. Seiler et al., Inhibition of polyamine oxidase enhances the cytotoxicity of polyamine oxidase substrates. A model study with N-1-(n-octanesulfonyl)spermine and human colon cancer cells, INT J BIO C, 32(7), 2000, pp. 703-716
Citations number
38
Categorie Soggetti
Biochemistry & Biophysics
Journal title
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
N-1-(n-octanesulfonyl)spermine (N-1 OSSpm) is a substrate of polyamine oxid
ase. It shares several properties with spermine, such as antagonism of NMDA
-type glutamate receptors, calmodulin antagonism, and cytotoxicity, but it
is more potent by orders of magnitude in these regards than spermine. The h
uman colon carcinoma-derived cell line CaCo-2 was used as a model to study
the toxicity of N-1 OSSpm as a function of polyamine oxidase (PAO) activity
and differentiation. If the formation of hydrogen peroxide and aminoaldehy
de by the PAO-catalysed reactions was prevented by selective inactivation o
f the enzyme with MDL 72527, cytotoxicity of N(1)OSSpm was not diminished,
but on the contrary, enhanced. Exponentially growing CaCo-2 cells were cons
iderably more sensitive to N(1)OSSpm than differentiating cells. The result
s suggest that cytotoxic substrates of PAO exhibit enhanced cytotoxicity in
cells, if PAO activity is inhibited. Since tumour cells are known to have
lower polyamine oxidase activities than their normal counterparts, it will
be interesting to explore whether cytotoxic substrates of polyamine oxidase
, for which N(1)OSSpm is an example, are suited to preferentially kill tumo
ur cells. (C) 2000 Elsevier Science Ltd. All rights reserved.