ArticleStrahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]2012
Radiosensitizing effect of epothilone B on human epithelial cancer cells.
Article in Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 13 citations in OpenAlex.
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- Radiosensitizing effects of trabectedin on human A549 lung cancer cells and HT-29 colon cancer cells.Investigational new drugs · 2020Article
- A genomic Multiprocess survey of machineries that control and link cell shape, microtubule organization, and cell-cycle progression.Developmental cell · 2014Article
- The effect of resveratrol in combination with irradiation and chemotherapy: study using Merkel cell carcinoma cell lines.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2014Article
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8 authors at 2 institutions in 1 country.
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Abstract
backgroundA 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.
methodsCancer 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.
resultsEpothilone B induced a concentration- and application-dependent antiproliferative effect on the cells, with IC(50) 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.
conclusionThe 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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