التفاصيل البيبلوغرافية
| العنوان: |
The topoisomerase inhibitors camptothecin and etoposide induce a CD95-independent apoptosis of activated peripheral lymphocytes. |
| المؤلفون: |
Ferraro, C, Quemeneur, L, Fournel, S, Prigent, A-F, Revillard, J-P, Bonnefoy-Berard, N |
| المصدر: |
Cell Death & Differentiation; Feb2000, Vol. 7 Issue 2, p197, 10p |
| مصطلحات موضوعية: |
DNA topoisomerase I, ISOMERASES |
| مستخلص: |
The effect of etoposide and 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[sup +] and CD8[sup +] T lymphocytes. Cell sensitivity to these agents required G[sub 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. [ABSTRACT FROM AUTHOR] |
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