Cycloheximide-induced apoptosis in Burkitt lymphoma (BJA-B) cells with and without Epstein-Barr virus infection.
Epstein-Barr virus (EBV) has been shown, in many instances, to protect B cells from apoptosis via expression of select EBV proteins and up-regulation of bcl-2 or its homologues. However, at present little is known about the influence of EBV infection against cancer therapy-induced apoptosis in EBV-associated cancers. Many anti-cancer treatments act via inhibition of protein synthesis and so could influence the reported protein-dependent mechanisms involved in EBV inhibition of apoptosis. In the present study, Burkitt lymphoma (BJA-B) cells were treated with a potent protein synthesis inhibitor, cycloheximide (CHX). Two variants of BJA-B cells were used, one with EBV infection (EBV(+)), and one free of infection (EBV(-)). Cells were collected 0,3,6,12, 24 and 48 h after addition of either 1 or 50 micrograms/mL of CHX. Control cultures were untreated. Apoptosis was quantified using established morphological and biochemical characteristics, and protein concentrations assessed. CHX treatment of EBV(-) BJA-B cells induced massive levels of apoptosis. Apoptosis was inhibited, but remained significantly higher than that found in control cultures, in similarly treated EBV(+) cells. The study demonstrates that induction of apoptosis in EBV(-) and EBV(+) cells is not dependent on new protein synthesis and so may be indicative of a bcl-2 independent mechanism in this instance. The results have important implications for devising and assessing treatment of EBV-associated malignancies.
Ishii
H H
HH
Department of Pathology, School of Medicine, Kitasato University, Sagamihara, Japan.
Etheridge
M R
MR
Gobé
G C
GC
D000963:Antimetabolites / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D003513:Cycloheximide / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000254:growth & development*; D006801:Humans; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D003513:Cycloheximide