Chenoufi N, Drénou B, Loréal O, Pigeon C, Brissot P, Lescoat G
Liver Research Unit, INSERM U49, Pontchaillou University Hospital, Rennes, France.
Biochem Pharmacol. 1998 Aug 15;56(4):431-7. 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 microM; 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 microM, 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.
铁是细胞代谢和所有生物生长所必需的元素，并且参与DNA复制。肝细胞癌发生的风险与铁可利用性的增加有关。本研究的目的是调查口服铁螯合剂去铁酮（CP20）对培养的HepG2细胞系增殖的影响。将HepG2细胞培养物在无胎牛血清（FCS）的情况下，以及在存在或不存在（对照培养物）浓度为50或100 microM的CP20的情况下进行培养；去铁胺（DFO）用作铁螯合剂对照。通过使用[3H]甲基胸腺嘧啶核苷掺入分析DNA合成以及通过流式细胞术分析细胞周期来研究细胞增殖。通过分析CP20对放射性铁摄取、细胞内铁蛋白水平和转铁蛋白受体表达的影响，研究培养模型中的铁螯合效率。浓度为50或100 microM的CP20在孵育48小时后抑制DNA合成，并诱导细胞在细胞周期的S期积累。铁螯合剂抑制细胞对铁的摄取，降低细胞内铁蛋白水平，并增加转铁蛋白受体蛋白和mRNA水平。我们的结果表明，CP20以及去铁胺抑制HepG2细胞增殖并使细胞周期阻滞在S期。
