Participation of Bax-α in IFN-α-Mediated Apoptosis in Daudi B Lymphoma Cells

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Abstract
Although interferon-α (IFN-α) has proved beneficial in the treatment of some tumors, the basis for this is still uncertain. In this study, we examined the effects of IFN-α on the growth of tumor cells in vitro, using the Daudi line of B lymphoma cells as a model. There was a dose-dependent accumulation of these cells in the G1 phase of the cell cycle 24–48 h from the time of exposure to IFN-α. This was followed between 48 h and 96 h by an increasing degree of apoptosis, as assessed by cell survival, propidium iodine staining, and transmission electron microscopy. Concomitantly with the apoptosis, there was the appearance of p 18 Bax-α, an apparently novel variant low molecular weight form of the p21 Bax-α found in normal cells. There was also a slight diminution in Bcl-xL, with a resultant drop in the Bcl-xL:Bax-α ratio. Treatment of cells with CD40-L partially inhibited the development of apoptosis in response to IFN-α. At the same time, generation of pl8 Bax-α was reduced, which suggests that this plays a part in the apoptotic process. These findings may throw light on the development of lymphomas and perhaps point to future ways of improving therapy with IFN-α.