Short-term exposure with high-dose interferon-α induces apoptosis in neuroblastoma cells in G0/G1 phase of the...

Type I interferons (IFNs) have been applied to immunotherapy for various malignancies, but therapeutic utilization for pediatric solid tumors has not been well established. IFN has short half-life in vivo, and it remains unclarified whether short-term exposure with IFN may results in tumoricidal outcomes. In the present study, we examined effects of IFN pulse treatment on neuroblastoma cells and analyzed cell-cycle dependency of the effects. Neuroblastoma cells underwent apoptosis after intermediate to high dose (10-100 IU/mL) continuous exposure, or a high dose (1000 IU/mL) pulse for 1 h, of recombinant human IFN-α (rhIFN-α). Repetitive pulse treatments with a high dose rhIFN-α reduced cell viability as remarkably as continuous treatment with the same dose of the cytokine. Cell-cycle analysis demonstrated a significant decrease in G0/G1 and G2/M cells and a remarkable increase in sub-G0/G1 cells after IFN pulse. Cell-cycle synchronization experiments revealed that IFN pulse at the G0/G1 phase induced apoptosis in the tumor cells, while that at the G2/M phase decelerated cell-cycle progression. These results suggest that short-term exposure with a high dose IFN may substantially suppress pediatric solid tumors, by inducing apoptosis in a cell-cycle dependent fashion.