Two different mechanisms of apoptosis resistance observed in interferon-β induced apoptosis of human glioma cells

Interferon (IFN)-β is known to exert cytostatic or cytocidal effects in human glioma cells and is widely used in the treatment for gliomas. However, precise mechanisms of cell death induced by IFN-β are not well understood. In this study, the authors investigated the intracellular signal transduction of IFN-β in human glioma cells. The cell death process observed in susceptible cells SK-MG-1 was accompanied by characteristic morphological changes of apoptosis, processing of caspases, and DNA fragmentation. Use of caspase inhibitors confirmed the activation of caspases, however activated executioner caspase was caspase-7 rather than caspases-3 or -6. Activation of DNA endonuclease, DNase-γ was also observed. Observation of other IFN-β relatively resistant glioma cells (U251SP, T98G, U251MG, U87MG, SK-AO2) revealed two different mechanisms of apoptosis resistance. In contrast to T98G, U87MG, and SK-AO2 which showed no activation of caspases, surprisingly, all the apoptosis process except DNase-γ activation was observed in U251SP and U251MG cells. Collectively, these findings indicate that IFN-β induced apoptosis in human glioma cells through activation of caspase-7 and activation of DNase-γ. The similar activations of caspases were found also in some of the apoptosis resistant cells. These findings may help to improve the IFN-β therapy in near future.