1,10-phenanthroline potentiates cytotoxicity of hydroxyurea in human chronic myeloid leukemia cells.
The effect of the divalent hydrophobic metal chelator 1,10-phenanthroline was evaluated alone and in combination with the antineoplastic agent hydroxyurea on human chronic myeloid leukemia cells. The compound at concentrations of 10 and 5 micrograms/ml significantly (p less than 0.001) potentiates DNA biosynthesis inhibiting the activity of hydroxyurea in vitro. Synergistic inhibition was obtained when both 1,10-phenanthroline and hydroxyurea was used in combination at relatively nontoxic concentrations. Cytotoxicity due to the combination was found to be partially reversible and was marginally reversible in the presence of Fe+2 and Zn. The results strongly suggest the utility of the iron-chelating agent along with hydroxyurea for further evaluation to achieve a better therapeutic result in the clinic.
Kamath
N S
NS
Cancer Research Institute, Tata Memorial Centre, Bombay, India.
Satyamoorthy
K
K
Chitnis
M P
MP
Advani
S H
SH
D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D007501:Iron; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects; D010618:Phenanthrolines / Q000494:pharmacology* / Q000627:therapeutic use; D015032:Zinc
D010618:Phenanthrolines; D004247:DNA; D007501:Iron; D015032:Zinc; C025205:1,10-phenanthroline; D006918:Hydroxyurea