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Effect of phenazine compounds XR11576 and XR5944 on DNA topoisomerases

Lookup NU author(s): Andrew Jobson, Dr Elaine Willmore, Dr Michael Tilby, Professor Caroline Austin

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Abstract

Purpose: Previous in vitro cleavage data showed that XR11576 and XR5944 stabilised topoisomerase I and topoisomerase II complexes on DNA in a dose-dependent fashion. However, some studies indicated a possible topoisomerase-independent mechanism of action for these drugs. Methods: Three methods, the TARDIS assay, immunoband depletion and the K+/SDS assay have been used to assess topoisomerase complex formation induced by XR11576 or XR5944 in human leukaemic K562 cells. Results: TARDIS and immunoband depletion assays demonstrated that XR11576 and XR5944 induced complex formation for both topoisomerase I and topoisomerase II (alpha and beta) in a dose- and time-dependent manner, following exposure times of 24 and 48 h at concentrations of 1 or 10 μM. The K+/SDS assay showed the formation of protein/DNA complexes after a 1 h exposure to 1 or 10 μM XR11576. Conclusion: Our data confirm that XR11576 or XR5944 can form topoisomerase complexes, after long periods of exposure. © 2008 Springer-Verlag.


Publication metadata

Author(s): Jobson, A., Willmore, E., Tilby, M.J., Mistry, P., Charlton, P, Austin, C.

Publication type: Article

Publication status: Published

Journal: Cancer Chemotherapy and Pharmacology

Year: 2008

Volume: 63

Issue: 5

Pages: 1-13

Print publication date: 01/01/2008

ISSN (print): 0344-5704

ISSN (electronic): 1432-0843

URL: http://dx.doi.org/10.1007/s00280-008-0812-9

DOI: 10.1007/s00280-008-0812-9


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