• Jérome Devy, Richard Wargnier, Michel Pluot, Igor Nabiev, and Alyona Sukhanova.
• EA no3306 Interactions Cellulaires et Moléculaires en Cancérologie, IFR no53 Biomolécules, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51100 Reims, France.
• Anticancer Res. 2004 May 1; 24 (3a): 1745-51.

BackgroundHuman DNA topoisomerase I (topo 1) is an essential nuclear enzyme involved in vital cellular processes and the sole target of antitumor drugs of the camptothecin (CPT) family. The CPT derivative topotecan (Tpt, Hycamtin) is currently used in clinic, its effectiveness varying considerably for different types of cancer. The purpose of this study was to compare time- and dose-dependent cellular responses to Tpt in terms of alterations in the amount and stability of topo 1 in lung adenocarcinoma (A-549), ovarian adenocarcinoma (CaOv-3), colorectal adenocarcinoma (HT-29) and breast adenocarcinoma (MCF-7) cell lines.Materials And MethodsWestern blot analysis of the time-dependent redistribution of a full-size topo 1 and its proteolytical fragments was performed after Tpt treatment for 1 h at concentrations 10-fold or 100-fold higher than the Tpt IC50 for the respective cell lines.ResultsTpt treatment of the CaOv-3 cell line produced a substantial time-dependent decrease in the amount of topo 1 immunoprotein. Conversely, the MCF7 cell line did not exhibit a topo 1-associated response to the Tpt treatment. Strong but different time- and dose-dependent topo 1 down-regulation effects were observed in the HT-29 and A-549 cell lines.ConclusionThe data obtained indicate that Tpt-induced time- and dose-dependent effects on the amount and stability of topo 1 are involved in the mechanisms of Tpt activity against different solid tumor cell lines.

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