Effect of pentoxifylline on apoptosis of cultured cells.
Apoptosis or programmed cell death (PCD) was measured in two human cell models by flow cytometric analysis. Blood neutrophils underwent spontaneous apoptosis in short-term culture. Pentoxifylline (PTX) inhibited spontaneous neutrophil PCD. We confirmed that granulocyte/macrophage colony-stimulating factor (GM-CSF) inhibited apoptosis of polymorphonuclear neutrophils. Treatment with both GM-CSF and PTX did not increase the inhibition of PCD by either GM-CSF or PTX alone. Because apoptosis could be due to the accumulation of H2O2 in the culture medium, and because PTX has been described to reduce peroxide production, we studied the effect of adding catalase to the medium. Catalase reduced the neutrophil apoptosis and this effect was cumulative with the effect of PTX. Camptothecin, an inhibitor of topoisomerase I, induces a block in the S-phase of the cell cycle followed by apoptosis of the U937 cell line. This drug-induced apoptosis was partially inhibited by PTX, whereas the S-phase cell block was not affected. In conclusion, PTX was found to inhibit apoptosis in two different human cell types. In neutrophils, this effect appears to occur regardless of the inhibition of phosphodiesterase activity and inhibition of H2O2 release.
Belloc
F
F
Laboratoire d' Hématologie, Hôpital Haut Lévêque, Pessac, France.
Jaloustre
C
C
Dumain
P
P
Lacombe
F
F
Lenoble
M
M
Boisseau
M R
MR
D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D002374:Catalase; D010431:Pentoxifylline