Cancer Chemotherapy and Pharmacology

, Volume 29, Issue 1, pp 48–52 | Cite as

The effect of staurosporine on drug-induced, topoisomerase II-mediated DNA cleavage in human leukemia cells

  • Leonard A. Zwelling
  • Elizabeth Altschuler
  • Janice Mayes
  • Michael Hinds
  • Diana Chan
Original Articles Topoisomerase II, Staurosporine, DNA Cleavage
Received:
Accepted:

Summary

Phorbol-12-myristate 13-acetate (PMA), a stimulator of protein kinase C, dramatically decreased topoisomerase II-reactive drug-induced DNA cleavage in HL-60 human cells. The effect of staurosporine, an inhibitor of protein kinase C, on drug-induced, topoisomerase II-mediated DNA cleavage was quantified in the same cells. Staurosporine decreased the magnitude of 4′-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA)- and etoposide-induced DNA cleavage in a dose-and time-dependent fashion. Measurement of several parameters of cell proliferation revealed no clear and uniform correlation between staurosporine's inhibition of these parameters and its effects on drug-induced DNA cleavage. A direct comparison with PMA's effects on drug-induced DNA cleavage showed that whereas PMA's inhibition of etoposide-induced cleavage was much greater than its inhibition ofm-AMSA-induced cleavage, the magnitude of staurosporine's effect on the cleavage produced by the two topoisomerase II-reactive drugs was similar. Thus, although PMA stimulates protein kinase C and staurosporine inhibits this enzyme, it is unlikely that the actions of either on topoisomerase II-reactive, drug-induced DNA cleavage are mediated directly via protein kinase C. Furthermore, it is likely that the mechanisms by which PMA and staurosporine inhibit topoisomerase II-reactive drug-induced cleavage are different.

Keywords

Cell Proliferation Leukemia Protein Kinase Human Cell Leukemia Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

m-AMSA

4′-(9-Acridinylamino)methanesulfon-m-anisidide; etoposide

VP-16

4′-demethylepipodiphyllotoxin 4-(4,6-O-ethylidene-β-d-glucopyranoside)

STSN

staurosporine

PMA

phorbol-12-myristate 13-acetate

DMSO

dimethylsulfoxide

AD

adherent cells

SN

supernatant cells

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Leonard A. Zwelling
    • 1
  • Elizabeth Altschuler
    • 1
  • Janice Mayes
    • 1
  • Michael Hinds
    • 1
  • Diana Chan
    • 1
  1. 1.Department of Medical Oncology, Division of MedicineThe University of Texas, M.D. Anderson Cancer CenterHoustonUSA

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