Microbial iron chelator-induced cell cycle synchronization in L1210 cells: potential in combination chemotherapy

Parabactin, a microbial iron chelator (a siderophore), is shown to be a more potent cell synchronization agent than either desferrioxamine or hydroxyurea. When the L1210 cell cycle is blocked with parabactin, cells are held at the G1-S border. If the ligand is later washed away, the block is reversed, and the cells cascade into S phase. The cells are synchronized through three cell cycles. The siderophore-induced block is exploited in the inhibition of growth of L1210 cells by combination with the antineoplastics, doxorubicin (Adriamycin), cytarabine, and bischloroethyl nitrosourea. The growth-inhibitory effects of Adriamycin, cytarabine, and bischloroethyl nitrosourea in combination with parabactin are shown to be dependent on the time frame in which the combination of drugs is presented to the cells. The results are in keeping with changes in L1210 cell cycle kinetics induced by the catecholamide chelator, parabactin.