Quaternary Benzo[c]phenanthridine Alkaloids as Inhibitors of
Dipeptidyl Peptidase IV-Like Activity Bearing Enzymes in Human
Blood Plasma and Glioma Cell Lines
A. ŠEDO1, R.
MALÍK1, J. VIČAR2, V. ŠIMÁNEK2,
J. ULRICHOVÁ2
1Laboratory of Cancer Cell Biology, Second
Institute of Medical Chemistry and Biochemistry, Charles
University, Prague, Czech Republic, 2Institute
of Medical Chemistry and Biochemistry, Palacký University,
Olomouc, Czech Republic
Received May 13, 2002
Accepted August 12, 2002
Summary
Quaternary benzo[c]phenanthridine alkaloids (QBA), fagaronine
(FA), sanguinarine (SA), chelerythrine (CHE) and the QBA extract
from Macleya cordata (EX) exerted differential inhibitory effect
on the hydrolytic activity of particular dipeptidyl peptidase (DPP)-like
enzyme isolated from human blood plasma and from human and rat
glioma cell lines. The low-MW form of DPP-IV-like enzyme
activity, corresponding most probably to DPP-8, observed only in
glioma cells but not in human plasma, was inhibited
preferentially by SA, CHE and EX, and only slightly by FA. The
alkaloid inhibitory effect was concentration-dependent in the
range 25-150 M and directly pH-related. In addition, a subtle
but consistent inhibition of the intermediate-MW form of DPP-IV-like
enzyme activity, ascribed to DPP-IV/CD26, observed only in human
plasma and of the attractin (high-MW form of DPP-IV-like enzyme
activity, expressed in U87 glioma cells) by the studied
alkaloids was observed. We conclude that some of the QBA
biological effects could be determined by tissue and cell type
specific dipeptidyl peptidase IV-like molecules expression
pattern.
Key
words
Fagaronine • Sanguinarine • Chelerythrine • Macleya
cordata • Dipeptidyl peptidase IV • Attracti
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Vilím Šimánek, Institute of Medical Chemistry and Biochemistry,
Faculty of Medicine, Palacký University, Hněvotínská 3, 775 15
Olomouc, Czech Republic, tel/fax: +420 685 632 302, e-mail:vilim@tunw.upol.cz
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