In vitro cytotoxicity of caracemide alone and in combination with hydroxyurea or iron-chelating agents in human chronic myeloid leukemia cells and murine tumors.

The cytotoxic effect of caracemide and hydroxyurea was compared in human chronic myeloid leukemia cells. Caracemide was found to be about twelve times more effective than hydroxyurea. The combined effect of caracemide, hydroxyurea and hydrophobic iron-chelating agents at relatively nontoxic concentrations was studied. Hydroxyurea, 2,2'-bipyridine and 1,10-phenanthroline combined with caracemide synergistically inhibited DNA synthesis, while Desferal did not show any such effect. Fe++ partially reversed the cytotoxicity of caracemide in combination with 2,2'-bipyridine, while it had no effect on the cytotoxicity of caracemide alone. Caracemide was found to have a stronger inhibitory effect on DNA synthesis in P388 lymphocytic leukemia and Ehrlich ascites carcinoma cells than hydroxyurea. However, bipyridine, phenanthroline and Desferal in combination with caracemide did not induce any synergistic inhibition. These data indicate the value of human tumor cells to predict drug responsiveness and suggest the further evaluation of caracemide and its combination with hydroxyurea and iron-chelating agents in the treatment of human leukemias.