Journal
CELL DEATH AND DIFFERENTIATION
Volume 7, Issue 2, Pages 197-206Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4400595
Keywords
apoptosis; caspase; camptothecin; ceramide; etoposide; peripheral blood lymphocytes
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The effect of etoposide acid camptothecin, two topoisomerase inhibitors directed against topoisomerases II and I, respectively, was evaluated on human peripheral blood lymphocytes, Etoposide and camptothecin induced apoptosis of mitogen-activated but not resting CD4(+) and CD8(+) T lymphocytes. Cell sensitivity to these agents required G(1) to S-phase transition of the cell cycle. Conversely, daunorubicin, an intercalating agent and topoisomerase II inhibitor, induced apoptosis of both resting and activated lymphocytes, Although etoposide and camptothecin induced CD95-ligand mRNA expression, drug-induced apoptosis of activated human lymphocytes was not inhibited by CD95 antagonists. Drug-induced cell death was also not inhibited by p55 TNFR-Ig fusion protein. Activation of the caspases cascade was suggested by the partial inhibitory effect of the tripeptide zVAD-fmk and documented by activation of caspase 3, Finally etoposide and camptothecin induced a rapid production of ceramide in activated but not resting peripheral blood lymphocytes, suggesting that ceramide might initiate the signaling apoptotic cascade in sensitive cells.
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