The anticancer activity of δ-tocotrienol, a bioactive vitamin E present in whole 
grain cereals, annatto beans and palm fruit, is strongly dependent on its effect 
on the induction of apoptosis. δ-Tocotrienol-induced apoptosis is associated 
with consistent induction in the expression of the proapoptotic protein 
Bcl-2-associated X protein (Bax). The molecular mechanism by which δ-tocotrienol 
regulates Bax expression is unknown. We carried out a DNA microarray study that 
identified δ-tocotrienol induction of the zinc finger transcription factor EGR-1 
in pancreatic cancer cells. Here, we provide evidence linking 
δ-tocotrienol-induced apoptosis in pancreatic cancer cells to EGR-1 regulation 
of Bax expression. Forced expression of EGR-1 induces Bax expression and 
apoptosis in pancreatic cancer cells. In contrast, knockdown of 
δ-tocotrienol-induced EGR-1 by small interfering RNA attenuated 
δ-tocotrienol-induced Bax expression and reduced δ-tocotrienol-induced 
apoptosis. Further analyses showed that de novo protein synthesis was not 
required for δ-tocotrienol-induced EGR-1 expression, suggesting a direct effect 
of δ-tocotrienol on EGR-1 expression. Furthermore, a chromatin 
immunoprecipitation assay demonstrated that EGR-1 binds to the Bax gene 
promoter. Finally, δ-tocotrienol treatment induced Bax expression and activated 
EGR-1 in the pancreatic neoplastic cells of the PDX-Cre Kras genetically 
engineered model of pancreatic cancer. Our study provides the first evidence for 
EGR-1 as a direct target of vitamin E δ-tocotrienol, suggesting that EGR-1 may 
act as a proapoptotic factor in pancreatic cancer cells via induction of Bax.