Neuroblastoma is a tumour derived from primitive cells of the sympathetic nervous system and is the most common extracranial solid tumour in childhood. Unfavourable tumours are characterised not only by structural changes, including 1p deletion and amplification of the MYCN proto-oncogene, but also by high
telomerase activity. Telomeric G-rich
single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to inhibit
telomerase activity. In this study, we examined
telomestatin, a G-quadruplex interactive agent, for its ability to inhibit telomere maintenance of
neuroblastoma cells. Telomere length was determined by the terminal restriction fragment method,
telomerase activity was measured by a quantitative telomeric repeat amplification protocol, and the expression of human
telomerase by quantitative real-time polymerase chain reaction (RT-PCR). Short-term treatment with
telomestatin resulted in dose-dependent cytotoxicity and induction of apoptosis. Long-term treatment with
telomestatin at non-cytotoxic, but still
telomerase activity-inhibiting, concentrations resulted in telomere shortening, growth arrest and induction of apoptosis. These results suggest that the effect of
telomestatin is dose-dependent and at least 2-fold. Prolonged low-dose treatment with
telomestatin limits the cellular lifespan of NB cells through disruption of telomere maintenance.