Modulation of cell proliferation and polyamine metabolism in rat liver cell cultures by the iron chelator O-trensox.
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.
Gaboriau
François
F
Inserm, U522, Hôpital Pontchaillou, F-35033, Rennes cedex, France.
Laupen-Chassay
Cindy
C
Pasdeloup
Nicole
N
Pierre
Jean-Louis
JL
Brissot
Pierre
P
Lescoat
Gérard
G
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005021:Ethylamines / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D013095:Spermidine / Q000494:pharmacology
D005021:Ethylamines; D006912:Hydroxyquinolines; D007502:Iron Chelating Agents; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C097548:trensox; D013095:Spermidine; D000518:Eflornithine