The 14-3-3 proteins are a family of regulatory molecules which are highly conserved among all eukaryotic cells. 14-3-3 proteins composed of seven isoforms which play crucial roles in regulating multiple cellular processes including the cell cycle regulation, DNA repair, apoptosis, cell adhesion and motility. Previously, we have reported that 14-3-3 epsilon protects endothelial and cancer cell survival via interacting with Bad and prevents its translocation to mitochondria. Nonsteroidal anti-inflammatory drugs (NSAIDs) induce endothelial and cancer cell apoptosis through suppressing 14-3-3 epsilon expression via a PPARd- dependent pathway. In this work, we propose to explore whether 14-3-3 protects cancer cells from bortezomib, a potent proteasome inhibitor based anti-cancer drug, -induced cell apoptosis. We discovered that bortezomib significantly reduces cancer cell viability and increases cleavage of PARP which suggest that bortezomib suppresses cancer cell survival and induces apoptosis in various types of cancer cells. Furthermore, bortezomib suppresses the expression of 14-3-3 epsilon in cancer cells. Stable cells constitutively overexpressing 14-3-3 epsilon significantly protects cell apoptosis induced by bortezomib. Taken together, these data reveal that 14-3-3 epsilon play as a potential targets for the prevention and therapy of tumor progression.
