RT Journal Article SR Electronic T1 Topotecan-induced Alterations in the Amount and Stability of Human DNA Topoisomerase I in Solid Tumor Cell Lines JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1745 OP 1752 VO 24 IS 3A A1 JÉROME DEVY A1 RICHARD WARGNIER A1 MICHEL PLUOT A1 IGOR NABIEV A1 ALYONA SUKHANOVA YR 2004 UL http://ar.iiarjournals.org/content/24/3A/1745.abstract AB Background: Human 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 Methods: Western 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. Results: Tpt 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. Conclusion: The 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. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved