Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-delta, nuclear factor kappaB, 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 microM) caused a significant increase in cellular proliferation exclusively at 72 h. Proliferation and cell viability were decreased in response to selenium concentrations of >/= 25 microM and >/= 5 microM at 72 and 96 h, respectively. Flow cytometric analysis of A20 cells exposed to 5 microM 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 microM phorbol 12-myristate 13-acetate (PMA) and Se (5 and 25 microM) 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 microM) at 72 h. After 72 h exposure to 5 and 25 microM 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.
Gopee
Neera V
NV
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, Georgia 30602-7389, USA.
Johnson
Victor J
VJ
Sharma
Raghubir P
RP
D000818:Animals; D016588:Anticarcinogenic Agents; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051745:Protein Kinase C-delta; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018038:Sodium Selenite / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D011506:Proteins; C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D018038:Sodium Selenite; D013755:Tetradecanoylphorbol Acetate