C-JUN INVOLVEMENT IN VITAMIN-E SUCCINATE INDUCED APOPTOSIS OF RETICULOENDOTHELIOSIS VIRUS-TRANSFORMED AVIAN LYMPHOID-CELLS

Previous studies have shown that treatment of avian reticuloendothelio sis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells with 10 mu g/ml (18.8 mu M) of RRR-alpha-tocopheryl succinate (vitamin E succi nate, VES) for 3 days induced approximately 50% of the cells to underg o apoptosis, Elevated and prolonged expression of c-jun mRNA and prote in was temporally correlated with VES-induced cell death, Data present ed in this paper show that the elevated and prolonged expression of c- jun message and protein are not accounted for by enhanced stability, a nd show the involvement of c-Jun in VES-induced apoptosis in this lymp hoblastoid cell type, C4-1 cells infected with a virus carrying a domi nant, negatively acting mutant form of c-Jun, supjun-1, exhibited: (i) 71% reduction in VES-induced apoptosis, (ii) a 2.0-2.5-fold decrease in wildtype, endogenous c-Jun expression, and (iii) a 2.4-2.6-fold red uction in AP-1 binding activity, Additionally, cells co-treated with V ES plus RRR-alpha-tocopherol, exhibited a 70% reduction in apoptosis, a marked reduction in c-Jun expression and a 1.6-fold reduction in AP- 1 binding activity, These studies suggest that c-Jun plays a crucial r ole in VES-induced apoptosis in C4-1 cells, and add to understanding o f mechanisms of action involved VES-mediated tumor cell growth inhibit ion.