Antiproliferative and iron chelating efficiency of the new bis-8-
hydroxyquinoline benzylamine chelator S1 in hepatocyte cultures.
Chem Biol Interact. 2012 Jan 25;195(2):165-72. Epub 2011 Dec 13.
Lescoat G, Léonce S, Pierré A, Gouffier L, Gaboriau F.
Inserm UMR 991, Foie, Métabolismes et Cancer, F-35033 Rennes, France;
Université de Rennes 1, F-35043 Rennes, France.

Abstract
If a new generation of iron chelators specifically devoted for cancer
chemotherapy emerged these last years, any of them has not yet been
approved at this time.
Accordingly, there is a need to optimize new chelating molecules for
iron chelation therapy and cancer treatment. So, the objective of the
present investigation was to characterize the antiproliferative
activity and the iron chelating capacity of the iron chelator S1 [bis-
N-(8-hydroxyquinoline-5-ylmethyl)benzylamine].
Its effects were compared to O-trensox which binds ferric iron with a
very high affinity (pFe(3+)=29.5).
For this purpose, primary rat hepatocyte stimulated by EGF and human
hepatoma HepaRG cell cultures were used.
In these models, the anti-proliferative effect, the inhibition of DNA
synthesis and the iron-chelating efficiency of increasing
concentrations of S1 and O-trensox (0 up to 200μM) were investigated.
In the two cell culture models, we observed that S1 was about 100
times more efficient than O-trensox and the antiproliferative effect
of S1 in HepaRG cells appeared at concentrations as low as 0.1μM
without cytotoxicity. Moreover, the stoichiometry of S1 for iron
seemed to be in the range S1/Fe(3+)=1.
Using the calcein fluorescence assay, we demonstrated that the
affinity of S1 for iron was better than that of O-trensox since it was
at least two times more effective to restore the fluorescence of
calcein previously quenched by iron.
So, the iron chelating efficiency of S1 could explain at least
partially its higher anti-proliferative effect compared to O-trensox.
Finally, these results suggest that molecules such as S1 may
constitute a promising starting point to improve cancer treatment.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID:22197641


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