Participation of Bax-alpha in IFN-alpha-mediated apoptosis in Daudi B lymphoma cells

Although interferon-alpha (IFN-alpha) 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-alpha 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-alpha. 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 pl8 Bax-alpha, an apparently novel variant low molecular weight form of the p21 Bax-alpha found in normal cells. There was also a slight diminution in Bcl-xL, with a resultant drop in the Bcl-xL:Bax-alpha ratio. Treatment of cells with CD40-L partially inhibited the development of apoptosis in response to IFN-alpha. At the same time, generation of p18 Bax-alpha 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-alpha.