ANTIPROLIFERATIVE EFFECT OF DEFERIPRONE ON THE HEP G2 CELL-LINE

Iron is an essential element in cellular metabolism and the growth of all living species, and is involved in DNA replication. The risk of he patocellular carcinoma development is associated with an increase in i ron availability. The aim of the present work was to investigate the e ffect of an oral iron chelator, deferiprone (CP20), on HepG2 cell-line proliferation in culture. HepG2 cell cultures were maintained in the absence of fetal calf serum (FCS) and in the presence or not (control cultures) of CP20 at the concentrations of 50 or 100 ELM; deferoxamine (DFO) was used as an iron chelator reference. Cell proliferation was investigated by the analysis of DNA synthesis using [H-3] methyl-thymi dine incorporation and of the cell cycle by flow cytometry. Iron chela tion efficiency in the culture model was studied by analyzing the effe ct of CP20 on radioactive iron uptake, intracellular ferritin level, a nd transferrin receptor expression. CP20, at the concentration of 50 o r 100 mu M, inhibited DNA synthesis after 48 hr of incubation and indu ced an accumulation of the cells in the S phase of the cell cycle. Iro n chelators inhibited cellular iron uptake, decreased intracellular fe rritin level, and increased transferrin receptor protein and mRNA leve ls. Our results show that CP20 as well as deferoxamine inhibit HepG2 c ell proliferation and block cell cycle in the S phase. BIOCHEM PHARMAC OL 56;4:431-437, 1998. (C) 1998 Elsevier Science Inc.