Suppression of HL-60 cell proliferation by deferoxamine: changes in c-myc expression.

Deferoxamine, an iron chelating agent, inhibits growth of HL-60 cells in a dose-dependent fashion. This inhibition of proliferation was completely blocked by simultaneous addition of equal molar FeCl3, and FeCl3 added after 24 hours of deferoxamine treatment was also effective. After 48 hrs, however, the delayed addition failed to reverse growth inhibition by deferoxamine. We showed that deferoxamine-treated HL-60 cells become arrested in S phase rather than at G1/0 phase. Changes in c-myc expression were examined in these deferoxamine-treated cells. A rapid decline of c-myc RNA expression was followed by increased expression (1.6-fold over untreated controls). Similar results were obtained when the expression of c-myc protein was evaluated. These changes in c-myc expression may be involved in the growth inhibition of HL-60 cells by deferoxamine. These results are contrasted with the effects of the differentiation inducer, 1 alpha,25(OH)2D3.