In vitro sequence-dependent synergistic effect of suramin and camptothecin

R. Lopez, G. J. Peters, E. Smitskamp-Wilms, J. A. Virizuela, J. van Ark-Otte, H. M. Pinedo, G. Giaccone

Research output: Contribution to journalArticle

Abstract

Suramin, a hexasulphonated naphthylurea with activity in prostatic cancer, possesses a wide variety of antitumour mechanisms of action, one of which is the inhibition of topoisomerase II. In this in vitro study, suramin was combined with the topoisomerase I inhibitor, camptothecin. Several suramin concentrations (0.2-3000 μM) were combined with camptothecin (0.4 pM-20 μM) in MCF-7 and PC3 human cancer cell line cultures. In addition, we studied the topoisomerase II and I gene expression by northern blot analysis, and the cell cycle distribution by flow cytometry, after exposure to suramin. While there was only an additive effect when suramin and camptothecin were added simultaneously, a remarkable synergism was obtained when camptothecin was added after a 3-day exposure to suramin. Topoisomerase II and I gene expression and the number of cells in S phase were significantly reduced after exposure to suramin. In conclusion, interaction of suramin with camptothecin is schedule-dependent can be synergistic. These findings might help in identifying optimal combinations of suramin or other topoisomerase II inhibitors, with topoisomerase I inhibitors.

Original languageEnglish (US)
Pages (from-to)1670-1674
Number of pages5
JournalEuropean Journal of Cancer
Volume30
Issue number11
DOIs
Publication statusPublished - 1994
Externally publishedYes

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Keywords

  • camptothecin
  • drug combination
  • suramin

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Lopez, R., Peters, G. J., Smitskamp-Wilms, E., Virizuela, J. A., van Ark-Otte, J., Pinedo, H. M., & Giaccone, G. (1994). In vitro sequence-dependent synergistic effect of suramin and camptothecin. European Journal of Cancer, 30(11), 1670-1674. https://doi.org/10.1016/0959-8049(94)00321-U