Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-δ, nuclear factor κB, and inhibitor of apoptosis protein

Selenium (Se) is an essential trace element possessing anticarcinogenic properties and other biological functions. This study determined the role sodium selenite plays on intracellular signaling, including protein kinase C (PKC), nuclear factor-kappa B (NF-kappaB), and inhibitor of apoptosis protein (IAP) in murine B lymphoma (A20) cells. In vitro supplementation of A20 cells with low concentrations of sodium selenite (0.005-5 muM) caused a significant increase in cellular proliferation exclusively at 72 h. Proliferation and cell viability were decreased in response to selenium concentrations of greater than or equal to 25 muM and greater than or equal to 5 muM at 72 and 96 h, respectively. Flow cytometric analysis of A20 cells exposed to 5 muM Se at 72 and 96 h indicated G(2)-M phase arrest and increased cell death at higher concentrations. Se-induced cytotoxicity was associated with apoptosis indicated by nuclear fragmentation and DNA laddering. Se concentrations, which induced cell cycle arrest and apoptosis, were associated with inhibition of cytosol to membrane translocation of PKCdelta and PKC activity at 72 h. Coincubation of cultures with 0.5 muM phorbol 12-myristate 13-acetate (PMA) and Se (5 and 25 muM) reversed the Se-induced cell death at 72 h. The nuclear NF-kappaB translocation and NF-kappaB DNA-binding were inhibited by increasing concentrations of Se (5 and 25 muM) at 72 h. After 72 h exposure to 5 and 25 muM Se, cIAP-2 concentration was decreased. Differential inhibition of PKCdelta, NF-kappaB, and cIAP-2 by Se may represent important intracellular signaling processes through which Se induces apoptosis and subsequently exerts its anticarcinogenic potential.