Antiproliferative effect of deferiprone on the Hep G2 cell line

• Published in: Biochemical pharmacology Vol. 56; no. 4; pp. 431 - 437
• Main Authors: Chenoufi, Norchen, Drénou, Bernard, Loréal, Olivier, Pigeon, Christelle, Brissot, Pierre, Lescoat, Gérard
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.08.1998; Elsevier Science
• Subjects: Antineoplastic agents; Biological and medical sciences; cell cycle; Cell Cycle - drug effects; Cell Division - drug effects; Chemotherapy; Deferiprone; deferoxamine; DNA - biosynthesis; DNA synthesis; HepG2 cell line; Humans; iron; Iron - metabolism; Iron Chelating Agents - pharmacology; Medical sciences; Pharmacology. Drug treatments; Pyridones - pharmacology; Tumor Cells, Cultured; deferiprone; iron; DNA synthesis; deferoxamine; cell cycle; HepG2 cell line; Human; Cell proliferation; Transferrin; Gene product; Ferritin; Hepatic disease; Hepatocellular carcinoma; Cytotoxicity; Deferiprone; Malignant tumor; Gene expression; In vitro; Deferoxamine; Iron ion; S Phase; Cell cycle; Established cell line; Tumor progression; Chelating agent; Digestive diseases; Tumor cell
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(98)00071-9

Iron is an essential element in cellular metabolism and the growth of all living species, and is involved in DNA replication. The risk of hepatocellular carcinoma development is associated with an increase in iron availability. The aim of the present work was to investigate the effect 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 μM; deferoxamine (DFO) was used as an iron chelator reference. Cell proliferation was investigated by the analysis of DNA synthesis using [ 3H] methyl-thymidine incorporation and of the cell cycle by flow cytometry. Iron chelation efficiency in the culture model was studied by analyzing the effect of CP20 on radioactive iron uptake, intracellular ferritin level, and transferrin receptor expression. CP20, at the concentration of 50 or 100 μM, inhibited DNA synthesis after 48 hr of incubation and induced an accumulation of the cells in the S phase of the cell cycle. Iron chelators inhibited cellular iron uptake, decreased intracellular ferritin level, and increased transferrin receptor protein and mRNA levels. Our results show that CP20 as well as deferoxamine inhibit HepG2 cell proliferation and block cell cycle in the S phase.