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Strahlentherapie und Onkologie

Published in:

01-02-2012 | Original article

Radiosensitizing effect of epothilone B on human epithelial cancer cells

Authors: T. Baumgart, G. Klautke, S. Kriesen, S.A. Kuznetsov, D.G. Weiss, R. Fietkau, G. Hildebrandt, K. Manda

Published in: Strahlentherapie und Onkologie | Issue 2/2012

Abstract

Background

A combined modality treatment employing radiation and chemotherapy plays a central role in the management of solid tumors. In our study, we examined the cytotoxic and radiosensitive effect of the microtubule stabilizer epothilone B on two human epithelial tumor cell lines in vitro and its influence on the microtubule assembly.

Methods

Cancer cells were treated with epothilone B in proliferation assays and in combination with radiation in colony-forming assays. For the analysis of ionizing radiation-induced DNA damage and the influence of the drug on its repair a γH2AX foci assay was used. To determine the effect of epothilone B on the microtubule assembly in cells and on purified tubulin, immunofluorescence staining and tubulin polymerization assay, respectively, were conducted.

Results

Epothilone B induced a concentration- and application-dependent antiproliferative effect on the cells, with IC₅₀ values in the low nanomolar range. Colony forming assays showed a synergistic radiosensitive effect on both cell lines which was dependent on incubation time and applied concentration of epothilone B. The γH2AX assays demonstrated that ionizing radiation combined with the drug resulted in a concentration-dependent increase in the number of double-strand breaks and suggested a reduction in DNA repair capacity. Epothilone B produced enhanced microtubule bundling and abnormal spindle formation as revealed by immunofluorescence microscopy and caused microtubule formation from purified tubulin.

Conclusion

The results of this study showed that epothilone B displays cytotoxic antitumor activity at low nanomolar concentrations and also enhances the radiation response in the tumor cells tested; this may be induced by a reduced DNA repair capacity triggered by epothilone B. It was also demonstrated that epothilone B in fact targets microtubules in a more effective manner than paclitaxel.

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Title: Radiosensitizing effect of epothilone B on human epithelial cancer cells
Authors: T. Baumgart
G. Klautke
S. Kriesen
S.A. Kuznetsov
D.G. Weiss
R. Fietkau
G. Hildebrandt
K. Manda
Publication date: 01-02-2012
Publisher: Springer Berlin Heidelberg
Published in: Strahlentherapie und Onkologie / Issue 2/2012
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-011-0029-4

At a glance: The STEP trials

Springer Medicine

Radiosensitizing effect of epothilone B on human epithelial cancer cells

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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