Preclinical investigation of combination from the telomerase–inhibitor BRACO 20 with cisplatin and the effects of sole BRACO 20 treatment on neuroblastoma cells

Aims: The combined use of telomerase inhibitors and cytostatic drugs might be a new approach in the treatment of neuroblastomas. We investigated if neuroblastoma cells react more sensitive to a combination of the telomerase inhibitor BRACO20 and Cisplatin (CDPP) than to CDPP alone. Materials and Methods: Experiments were carried out with the neuroblastoma cell lines KCN and SHEP-SF. Toxicity of BRACO20 and/or CDDP was determined by the MTT-test, telomere length by southern blot and telomerase activity (TA) by the TRAP-assay and a new real-time PCR method. Results: BRACO20 reduced the cell viability of KCN and SHEP-SF in a time and dose dependent manner. Pretreatment with non-toxic concentrations of BRACO20 for 24h as well as several weeks did not increase the toxicity of CDPP in KCN and SHEP-SF. BRACO20 treatment over several weeks decreased the growth of KCN cells, but TA and telomere length of KCN cells were not affected by BRACO20. Conclusion: Since BRACO20 did not influence TA and telomere length at the tested concentrations, the observed effects might be contributed to unspecific toxicity of BRACO 20. supported by the IZKF 3H2