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Modulation of cell proliferation and polyamine metabolism in rat liver cell cultures by the iron chelator O-trensox

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Abstract

The antiproliferative effects of the iron chelator O-trensox and the ornithine-decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) were characterized in the rat hepatoma cell line FAO, the rat liver epithelial cell line (RLEC) and the primary rat hepatocyte cultures stimulated by EGF. We observed that O-trensox and DFMO decreased cell viabilty and DNA replication in the three culture models. The cytostatic effect of O-trensox was correlated to a cytotoxicity, higher than for DFMO, and to a cell cycle arrest in G0/G1 or S phases. Moreover, O-trensox and DFMO decreased the intracellular concentration of spermidine in the three models without changing significantly the spermine level. We concluded that iron, but also polyamine depletion, decrease cell growth. However, the drop in cell proliferation obtained with O-trensox was stronger compared to DFMO effect. Altogether, our data provide insights that, in the three rat liver cell culture models, the cytostatic effect of the iron chelator O-trensox may be the addition of two mechanisms: iron and polyamine depletion.

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Authors and Affiliations

  1. Inserm, U522, Hôpital Pontchaillou, F-35033, Rennes cedex, France

    François Gaboriau, Cindy Laupen-Chassay, Nicole Pasdeloup, Pierre Brissot & Gérard Lescoat

  2. Univ Rennes 1, F-35000, Rennes cedex, France

    François Gaboriau, Cindy Laupen-Chassay, Nicole Pasdeloup, Pierre Brissot & Gérard Lescoat

  3. IFR 140, Rennes cedex, F-35000, France

    François Gaboriau, Cindy Laupen-Chassay, Nicole Pasdeloup, Pierre Brissot & Gérard Lescoat

  4. CNRS, UMR 5616, Univ Grenoble, F-38000, Grenoble, France

    Jean-Louis Pierre

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  1. François Gaboriau
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  2. Cindy Laupen-Chassay
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  3. Nicole Pasdeloup
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  4. Jean-Louis Pierre
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  5. Pierre Brissot
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  6. Gérard Lescoat
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Correspondence to Gérard Lescoat.

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Gaboriau, F., Laupen-Chassay, C., Pasdeloup, N. et al. Modulation of cell proliferation and polyamine metabolism in rat liver cell cultures by the iron chelator O-trensox. Biometals 19, 623–632 (2006). https://doi.org/10.1007/s10534-006-6888-y

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  • DOI: https://doi.org/10.1007/s10534-006-6888-y

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