Ontology type: schema:ScholarlyArticle
2009-12-08
AUTHORSFrançois Gaboriau, Anne-Marie Leray, Martine Ropert, Lucie Gouffier, Isabelle Cannie, Marie-Bérengère Troadec, Olivier Loréal, Pierre Brissot, Gérard Lescoat
ABSTRACTTwo 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. More... »
PAGES231-245
http://scigraph.springernature.com/pub.10.1007/s10534-009-9281-9
DOIhttp://dx.doi.org/10.1007/s10534-009-9281-9
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/19997770
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