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Interferon-gamma (IFN-gamma) has a well known differentiation-promoting activity on several neuroblastoma (NB) cell lines and has also been reported to induce apoptosis in different cellular models. We have investigated the potential of IFN-gamma to trigger, besides differentiation, programmed cell death in NB cells and the relationship between these processes. Nine NB cell lines, characterized by different phenotypic and maturational features, were cultured in the presence of IFN-gamma (1000 IU/ml) for up to 5 days with either only one treatment at the start of the culture or renewing the culture medium (with or without IFN-gamma) every other day. Neuronal differentiation was assessed by evaluation of morphological changes and expression of mature cytoskeletal proteins, while apoptosis was evaluated at the desired times by fluorescent and electronic microscopy, DNA content analysis and DNA fragmentation assay. Our findings show that apoptosis is an early (mainly non post-differentiative) event and is much more evident following a single IFN-gamma administration. Moreover, IFN-gamma-triggered apoptosis is independent of the cellular phenotype (schwannian or neuronal) and appears to be mutually exclusive with respect to differentiation at the single cell level. Our results strengthen the potential of IFN-gamma as a promising therapeutic agent for NB.

Induction of differentiation and apoptosis by interferon-γ in human neuroblastoma cells in vitro as a dual and alternative early biological response