Deferoxamine arrests in vitro the proliferation of porcine hepatocyte in G1 phase of the cell cycle.
Iron is required for cell proliferation of all living species. Moreover, iron excess may be involved in the development of hepatocellular carcinoma. In this study we analyzed the effects of deferoxamine, an iron chelator, on normal porcine hepatocyte proliferation. We confirmed that hepatocytes isolated from young pigs proliferate in the presence of insulin and fetal calf serum as shown by [3H] methyl-thymidine incorporation, presence of mitotic figures and increase in cell number. This was paralleled by nuclear expression of p34cdc2 and its associated histone H1 kinase activity. In the presence of deferoxamine, [3H] methyl-thymidine incorporation, expression of nuclear proteins (p34cdc2 and PCNA) and H1 kinase activity were drastically reduced. In addition, in contrast with control cultures, cells in S-phase were not detected by flow cytometry. These data suggest that iron chelation by deferoxamine can arrest the progression of porcine hepatocytes in the G1 phase of the cell cycle.
Chenoufi
N
N
INSERM U 49, Unité de Recherches Hépatologiques, CHRU Pontchaillou, Rennes, France.
Baffet
G
G
Drénou
B
B
Cariou
S
S
Desille
M
M
Clément
B
B
Brissot
P
P
Lescoat
G
G
Loréal
O
O
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D013552:Swine; D013778:Tetrazolium Salts / Q000378:metabolism
D005562:Formazans; D007502:Iron Chelating Agents; D018809:Proliferating Cell Nuclear Antigen; D013778:Tetrazolium Salts; C079782:MTT formazan; D004247:DNA; D007770:L-Lactate Dehydrogenase; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase; D003676:Deferoxamine