Ewing sarcoma is a rare
malignancy occurring in childhood and adolescence which has a prognosis of about 50% long-term event-free survival, depending on risk factors such as
tumor volume, initial
metastases at the time of diagnosis and
tumor response to presurgical
chemotherapy. In order to tailor
therapy to the individual patient, new prognostic factors need to be identified. In this study, we showed that
etoposide and
actinomycin D kill
Ewing tumor cells (RD-ES cell line) mainly via a
caspase-dependent mechanism. Both drugs induced a significant
caspase-3 activation, which can be detected with a new
caspase-3 assay. Dose-response analyses showed that induction of cell death and
caspase-3 activation is mediated by similar concentration ranges of both drugs. In addition to the cell line,
caspase-3 activation was also shown during
drug-mediated stimulation of freshly isolated cells from
tumor biopsies. In conclusion,
actinomycin D and
etoposide stimulated
caspase-3 activation in a
Ewing tumor cell line and in freshly isolated
tumor cells, causing
drug-induced cell death. Thus, determination of
caspase-3 activation might be a suitable method for
drug sensitivity testing in patients with Ewing
tumors before initiating treatment. This assay could therefore help individualize
therapy in future
tumor patients.