Potentiation of hydroxyurea cytotoxicity in human chronic myeloid leukemia cells by iron-chelating agent.
The effect of hydroxyurea (HU) was studied in 15 cases of human chronic myeloid leukemia cells (CML) in combination with iron-chelating agent, 2,2-bipyridine (bipyridine). The extent of (3H)thymidine incorporation in CML cells in vitro was taken as an index for the measurement of cytotoxicity. In the present study, we observed a potentiation in HU cytotoxicity by hydrophobic iron-chelator bipyridine (p less than 0.001) resulting in complete DNA biosynthesis inhibition. Both HU and bipyridine were used at a relatively non-toxic concentrations of 10(-4) M and 10 micrograms/ml, respectively. This inhibition was found to be partially reversible and a partial protective action by iron is also demonstrated. The various other metal chelators failed to sensitise CML cells to HU cytotoxicity. Implications with respect to the efficacy in cancer treatment is discussed.
D015082:2,2'-Dipyridyl / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use; D004357:Drug Synergism; D004492:Edetic Acid / Q000627:therapeutic use; D006801:Humans; D062385:Hydroxybenzoates / Q000627:therapeutic use; D006918:Hydroxyurea / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use*
D062385:Hydroxybenzoates; D011725:Pyridines; D015082:2,2'-Dipyridyl; C009135:2,3-dihydroxybenzoic acid; D004492:Edetic Acid; D003676:Deferoxamine; D006918:Hydroxyurea