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.
Epothilone B was shown to have promising chemo- and radiosensitizing effects on cells, but the mechanisms underlying cell death remain ambiguous. The aim of the study was to examine selected cell death pathways on the basis of FaDu and A549 cells. Western blot analyses were used for investigation of specific apoptotic markers. Immunofluorescence imaging and flow cytometry were utilized for examination of cell death mechanisms. DNA-staining was used for studying influence of epothilone B on micronucleus rate. We showed that epothilone B can initiate cell death via apoptosis and mitotic catastrophe, but induction of cell death was cell type specific.
In recent studies, epothilone B was shown to have a cytotoxic and radiosensitizing effect on cells. The aim of our investigation was to explain this impact by examining the mode of action of epothilone B on FaDu and A549 tumor cells. Flow cytometry was used for cell cycle distribution and for the evaluation of apoptosis. Metabolic activity was studied by proliferation assay. Influence on nuclei morphology was investigated by DNA-staining. We showed that epothilone B-induced G2/M accumulation is the main rationale for drug-induced radiosensitivity. The cytotoxic effect resulted in apoptotic cell death, decreased metabolic activity, and formation of multinucleated cells.
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