NDLI: Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG

Content Provider	Springer Nature Link
Author	Gaboriau, François Leray, Anne Marie Ropert, Martine Gouffier, Lucie Cannie, Isabelle Troadec, Marie Bérengère Loréal, Olivier Brissot, Pierre Lescoat, Gérard
Copyright Year	2009
Abstract	Two oral chelators, CP20 (deferiprone) and ICL670 (deferasirox), have been synthesized for the purpose of treating iron overload diseases, especially thalassemias. Given their antiproliferative effects resulting from the essential role played by iron in cell processes, such compounds might also be useful as anticancer agents. In the present study, we tested the impact of these two iron chelators on iron metabolism, in the HepaRG cell line which allowed us to study proliferating and differentiated hepatocytes. ICL670 uptake was greater than the CP20 uptake. The iron depletion induced by ICL670 in differentiated cells increased soluble transferrin receptor expression, decreased intracellular ferritin expression, inhibited 55Fe (III) uptake, and reduced the hepatocyte concentration of the labile iron pool. In contrast, CP20 induced an unexpected slight increase in intracellular ferritin, which was amplified by iron-treated chelator exposure. CP20 also promoted Fe(III) uptake in differentiated HepaRG cells, thus leading to an increase of both the labile pool and storage forms of iron evaluated by calcein fluorescence and Perls staining, respectively. In acellular conditions, compared to CP20, iron removing ability from the calcein-Fe(III) complex was 40 times higher for ICL670. On the whole, biological responses of HepaRG cells to ICL670 treatment were characteristic of expected iron depletion. In contrast, the effects of CP20 suggest the potential involvement of this compound in the iron uptake from the external medium into the hepatocytes from the HepaRG cell line, therefore acting like a siderophore in this cell model.
Starting Page	231
Ending Page	245
Page Count	15
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	23
Issue Number	2
e-ISSN	15728773
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-12-08
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Iron chelation Iron metabolism Siderophore Hepatocytes HepaRG cell line Cell proliferation Physical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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