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Topotecan-induced alterations in the amount and stability of human DNA topoisomerase I in solid tumor cell lines.
Anticancer Res. 2004 May-Jun; 24(3a):1745-51.AR

Abstract

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.

Authors+Show Affiliations

EA no3306 Interactions Cellulaires et Moléculaires en Cancérologie, IFR no53 Biomolécules, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51100 Reims, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15274350

Citation

Devy, Jérome, et al. "Topotecan-induced Alterations in the Amount and Stability of Human DNA Topoisomerase I in Solid Tumor Cell Lines." Anticancer Research, vol. 24, no. 3a, 2004, pp. 1745-51.
Devy J, Wargnier R, Pluot M, et al. Topotecan-induced alterations in the amount and stability of human DNA topoisomerase I in solid tumor cell lines. Anticancer Res. 2004;24(3a):1745-51.
Devy, J., Wargnier, R., Pluot, M., Nabiev, I., & Sukhanova, A. (2004). Topotecan-induced alterations in the amount and stability of human DNA topoisomerase I in solid tumor cell lines. Anticancer Research, 24(3a), 1745-51.
Devy J, et al. Topotecan-induced Alterations in the Amount and Stability of Human DNA Topoisomerase I in Solid Tumor Cell Lines. Anticancer Res. 2004 May-Jun;24(3a):1745-51. PubMed PMID: 15274350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topotecan-induced alterations in the amount and stability of human DNA topoisomerase I in solid tumor cell lines. AU - Devy,Jérome, AU - Wargnier,Richard, AU - Pluot,Michel, AU - Nabiev,Igor, AU - Sukhanova,Alyona, PY - 2004/7/28/pubmed PY - 2004/9/11/medline PY - 2004/7/28/entrez SP - 1745 EP - 51 JF - Anticancer research JO - Anticancer Res. VL - 24 IS - 3a N2 - 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. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/15274350/Topotecan_induced_alterations_in_the_amount_and_stability_of_human_DNA_topoisomerase_I_in_solid_tumor_cell_lines_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=15274350 DB - PRIME DP - Unbound Medicine ER -