The effect of desferrioxamine on cell proliferation in human tumour cell lines

Iron is known to have a stimulatory effect on cell proliferation whereas the iron-complexing agent desferrioxamine (DFO) has an inhibitory influence on the growth of cultured cells. The effect of iron salts and DFO on cell proliferation and DNA synthesis was studied on two established human tumour cell lines, a colon carcinoma (Caco-2) and a hepatoma-derived cell line (Hep.G2). Cell proliferation was estimated by the neutral red method, DNA synthesis by measuring the [(3)H]thymidine incorporation into the cells. For the analysis of the cell cycle the cells were marked with bromodeoxyuridine for S-phase cells and the monoclonal antibody Ki-67 for all proliferating cells. Ferric chloride stimulated cell proliferation in the Caco-2 line whereas there was no effect in the Hep.G2 line. DFO inhibited cell proliferation and DNA synthesis in both cell lines. Cell cycle analysis revealed a prolongation of the cell cycle by DFO, thereby reducing the number of cells entering the proliferating phases of the cell cycle in both cell lines. The data support the essential role of iron in cell proliferation and tumour growth.