alpha-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation

alpha-Tocopheryl succinate (alpha-TOS), but not alpha-tocopherol, triggered apoptosis in Jurkat T cells. Apoptosis was induced by alpha-TOS in a time- and concentration-dependent mode, and signs of apoptosis were visible at c oncentrations of alpha-TOS as low as 30 mu M, and within 3-5 h after additi on of the ester, Employing a specific fluorogenic substrate, caspase-3 was found to be activated rapidly in response to alpha-TOS at 50 mu M. We also found that Jurkat T cells challenged with alpha-TOS, when exposed to the ly sosomotropic weak base acridine orange, showed decreased lysosomal uptake o f the dye, This is suggestive of the involvement of lysosomal destabilisati on in apoptosis of the cells. Apoptosis of Jurkat T cells induced with alph a-TOS also involved a drop in the mitochondrial membrane potential, althoug h this phenomenon occurred after the initiation of lysosomal rupture. All a poptotic features observed with alpha-TOS were very similar to those found when cross-linking of the Fas receptor triggered apoptosis, These findings are consistent with the recent idea that vitamin E can contribute to elimin ation of malignant cells by the induction of apoptosis, and can be of (path o)physiological significance. (C) 1999 Federation of European Biochemical S ocieties.