c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells.
Previous studies have shown that treatment of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells with 10 microg/ml (18.8 microM) of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for 3 days induced approximately 50% of the cells to undergo apoptosis. Elevated and prolonged expression of c-jun mRNA and protein was temporally correlated with VES-induced cell death. Data presented in this paper show that the elevated and prolonged expression of c-jun message and protein are not accounted for by enhanced stability, and show the involvement of c-Jun in VES-induced apoptosis in this lymphoblastoid cell type. C4-1 cells infected with a virus carrying a dominant, 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 reduction in AP-1 binding activity. Additionally, cells co-treated with VES 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 role in VES-induced apoptosis in C4-1 cells, and add to our understanding of mechanisms of action involved in VES-mediated tumor cell growth inhibition.
Qian
M
M
Genetics Institute, Academy of Sciences of Czech Republic, Prague.
Kralova
J
J
Yu
W
W
Bose
H R
HR
Dvorak
M
M
Sanders
B G
BG
Kline
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D008214:Lymphocytes / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D001356:Reticuloendotheliosis virus / Q000235:genetics*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014810:Vitamin E; D024505:Tocopherols