Synergistic growth inhibitory and differentiating effects of trimidox and tiazofurin in human promyelocytic leukemia HL-60 cells

DOI PDF 被引用文献1件
  • T Szekeres
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • M Fritzer
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • H Strobl
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • K Gharehbaghi
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • G Findenig
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • HL Elford
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • C Lhotka
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • HJ Schoen
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.
  • HN Jayaram
    Institute of Medical Chemistry, University of Vienna Medical School, Ca 51770.

書誌事項

公開日
1994-12-15
DOI
  • 10.1182/blood.v84.12.4316.bloodjournal84124316
公開者
American Society of Hematology

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説明

<jats:p>Increased ribonucleotide reductase (RR) activity has been linked with malignant transformation and tumor cell growth. Therefore, this enzyme is considered to be an excellent target for cancer chemotherapy. We have examined the effects of a newly patented RR inhibitor, trimidox (3,4,5-trihydroxybenzohydroxamidoxime). Trimidox inhibited the growth of human promyelocytic leukemia HL-60 cells with an IC50 of 35 mumol/L. Incubation of HL-60 cells with 50 mumol/L trimidox for 24 hours decreased deoxyguanosine triphosphate (dGTP) and deoxycytidine triphosphate (dCTP) pools to 24% and 39% of control values, respectively. Incubation of HL-60 cells with 20 to 80 mumol/L trimidox even up to a period of 4 days did not alter the distribution of cells in different phases of cell cycle. Sequential incubation of HL-60 cells with trimidox (25 mumol/L) for 24 hours and then with 10 mumol/L tiazofurin (an inhibitor of inosine monophosphate dehydrogenase) for 4 days produced synergistic growth inhibitory activity, and the cell number decreased to 16% of untreated controls. When differentiation- linked cell surface marker expressions were determined in cells treated with trimidox and tiazofurin, a significantly increased fluorescence intensity was observed for the CD 11b (2.9-fold). CD 33 (1.9-fold), and HLA-D cell surface antigens. Expression of the transferrin receptor (CD71) increased 7.3-fold in cells treated with both agents, compared with untreated controls. Our results suggest that trimidox in combination with tiazofurin might be useful in the treatment of leukemia.</jats:p>

収録刊行物

  • Blood

    Blood 84 (12), 4316-4321, 1994-12-15

    American Society of Hematology

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