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Paper| Volume 30, ISSUE 11, P1670-1674, 1994

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In vitro sequence-dependent synergistic effect of suramin and camptothecin

DOI:https://doi.org/10.1016/0959-8049(94)00321-U
In vitro sequence-dependent synergistic effect of suramin and camptothecin
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      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.

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      Article info

      Publication history

      Accepted: June 21, 1994
      Received: June 13, 1994

      Identification

      DOI: https://doi.org/10.1016/0959-8049(94)00321-U

      Copyright

      © 1994 Published by Elsevier Inc.

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