xr5944 and Breast-Neoplasms

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.. 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.. 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 microM. The K(+)/SDS assay showed the formation of protein/DNA complexes after a 1 h exposure to 1 or 10 muM XR11576.. Our data confirm that XR11576 or XR5944 can form topoisomerase complexes, after long periods of exposure.

Topics: Animals; Breast Neoplasms; Cells, Cultured; CHO Cells; Colorectal Neoplasms; Cricetinae; Cricetulus; DNA Damage; DNA Repair; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Fluorescent Antibody Technique; Histones; Humans; Immunoassay; K562 Cells; Phenazines; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors