ToxSci Advance Access originally published online on January 21, 2004
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Toxicological Sciences 78, 204-214 (2004)
Toxicological Sciences vol. 78 no. 2 © Society of Toxicology; all rights reserved.
Sodium Selenite-Induced Apoptosis in Murine B-Lymphoma Cells Is Associated with Inhibition of Protein Kinase C-
, Nuclear Factor 
B, and Inhibitor of Apoptosis Protein
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, Georgia 30602-7389
Received October 30, 2003; accepted January 2, 2004
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-
B), 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 µM) caused a significant increase in cellular proliferation exclusively at 72 h. Proliferation and cell viability were decreased in response to selenium concentrations of 
25 µM and 5 µM at 72 and 96 h, respectively. Flow cytometric analysis of A20 cells exposed to 5 µM Se at 72 and 96 h indicated G2-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 PKC
and PKC activity at 72 h. Coincubation of cultures with 0.5 µM phorbol 12-myristate 13-acetate (PMA) and Se (5 and 25 µM) reversed the Se-induced cell death at 72 h. The nuclear NF-B translocation and NF-B DNA-binding were inhibited by increasing concentrations of Se (5 and 25 µM) at 72 h. After 72 h exposure to 5 and 25 µM Se, cIAP-2 concentration was decreased. Differential inhibition of PKC, NF-B, and cIAP-2 by Se may represent important intracellular signaling processes through which Se induces apoptosis and subsequently exerts its anticarcinogenic potential.
Key Words: selenium; phorbol 12-myristate 13-acetate; protein kinase C-; nuclear factor-B; cellular inhibitor of apoptosis protein-2.
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