Département de chimie moléculaire

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 obsd. that O-trensox and DFMO decreased cell viability and DNA replication in the 3 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 concn. of spermidine in the 3 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 3 rat liver cell culture models, the cytostatic effect of the iron chelator O-trensox may be the addn. of 2 mechanisms: iron and polyamine depletion. [on SciFinder(R)]