Cell cycle-dependent inhibition of the proliferation of human neural tumor cell lines by iron chelators.

The current studies were designed to examine the conditions under which the ferric iron chelator desferrioxamine (DFO) arrested cell cycle progression and hence the proliferation of neural cell lines in vitro. DFO arrested proliferation at different stages of the cell cycle depending on the concentration and duration of drug exposure. Twenty-four-hour treatment with 160 microM DFO arrested glioma cells in G1, whereas 72-hr treatment with 10 microM DFO acted to slow the passage of glioma cells through the cell cycle, eventually accumulating in G2/M. Another iron chelator, ADR 529, also inhibited the proliferation of glioma cells by lengthening the period of the cycle and causing the cells to arrest in G2/M. The effects of 10 and 160 microM DFO were irreversible after 24 and 48 hr, respectively, and 10 microM DFO became cytotoxic after 3 days. These observations demonstrate that DFO has different effects on the proliferation of neural tumor cell lines depending on the concentration and time of exposure, which result in different sites of cell cycle arrest. These different in vitro actions of DFO may have ramifications for the successful application of iron chelator therapy in vivo.