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Ceramide-induced killing of normal and malignant human lymphocytes is by a non-apoptotic mechanism

Mengubas, K; Riordan, FA; Bravery, CA; Lewin, J; Owens, DL; Mehta, AB; Hoffbrand, AV; (1999) Ceramide-induced killing of normal and malignant human lymphocytes is by a non-apoptotic mechanism. ONCOGENE , 18 (15) 2499 - 2506.

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Abstract

Synthetic ceramides induce apoptotic death of Jurkat and HL60 leukaemia cell lines. By contrast we show here that ceramide induces non-apoptotic killing of malignant cells from patients with B-chronic lymphocytic leukaemia (B-CLL) and of normal B lymphocytes, The protein phosphatase inhibitor okadaic acid readily induces apoptosis of B-CLL cells, indicating that this death pathway is fully functional in these cells. The ability of ceramide to activate the apoptotic protease caspase 3 in HL60 cells but not in B-CLL cells, as well as the lack of correlation of ceramide-mediated killing of different B-CLL isolates with expression of the apoptosis-regulating proteins bcl-2 and bax reinforce the conclusion that ceramide killing of B-CLL cells is by a non-apoptotic mechanism. Fludarabine treatment or gamma-irradiation of B-CLL cells resulted in ceramide elevation and in killing by both apoptotic and non-apoptotic mechanisms, suggesting that a ceramide-triggered non-apoptotic mechanism may play a role in the killing of these cells. Therefore, the results here show that ceramide can induce either apoptotic or non-apoptotic death, depending on the cellular conte it. The inability of synthetic dihydroceramide to kill B-CLL cells or normal B lymphocytes suggests that non-apoptotic killing by ceramide is via interaction with a specific, but unidentified, cellular target.

Type: Article
Title: Ceramide-induced killing of normal and malignant human lymphocytes is by a non-apoptotic mechanism
Keywords: ceramide, leukaemia, apoptosis, necrosis, RADIATION-INDUCED APOPTOSIS, DAUNORUBICIN-INDUCED APOPTOSIS, ACTIVATED PROTEIN-KINASES, CELL-DEATH, HL-60 CELLS, DNA-DAMAGE, IN-VITRO, B-CELL, LEUKEMIA, RESISTANCE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/138513
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