Selective inhibition of apoptosis by TPA-induced differentiation of U937 leukemic cells (original) (raw)

• Original Paper
• Published: 09 April 1999
• Ali Bettaieb1,
• Jean-Marie Bruey1,
• Béatrice Eymin1,
• Nathalie Droin1,
• Michael Ivarsson1,
• Carmen Garrido1 &
• …
• Eric Solary1

Cell Death & Differentiation volume 6, pages 351–361 (1999)Cite this article

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Abstract

U937 leukemic cells treated for 24 h with 16 nM 12-**O**-tetradecanoylphorbol 13-acetate (TPA), that induces their macrophagic terminal differentiation, become resistant to etoposide-induced apoptosis. Exposure of undifferentiated U937 cells to 50 μM etoposide for 6 h, that triggers apoptosis in 80% cells, activates procaspase-2L, -3 and -8, induces the mitochondrial release of cytochrome c and decreases Mcl-1 expression without modifying Bcl-2, Bcl-xL and Bax protein levels. All these events are inhibited in TPA-differentiated U937 cells that are also resistant to vinblastine-induced and Fas-mediated cell death. Interestingly, these cells are not inherently resistant to apoptosis induction. Exposure of TPA-differentiated U937 cells to 0.8 μg/ml cycloheximide for 24 h, that triggers apoptosis in 50% cells, activates procaspase-2L, -3 and -8, induces the mitochondrial release of cytochrome c and decreases Bcl-xL expression without modifying Bcl-2, Mcl-1 and Bax protein levels. All these events are not observed in undifferentiated cells treated in similar conditions. These results indicate that the apoptotic pathway that involves the release of cytochrome c from mitochondria and the cleavage of procaspases remains functional in TPA-differentiated cells.

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1. Department of Biology and Therapy of Cancer, INSERM U517, JE 515, Faculty of Medicine & Pharmacy, 7, boulevard Jeanne d'Arc, Dijon, 21033, France
   Olivier Sordet, Ali Bettaieb, Jean-Marie Bruey, Béatrice Eymin, Nathalie Droin, Michael Ivarsson, Carmen Garrido & Eric Solary

Authors

1. Olivier Sordet
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2. Ali Bettaieb
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3. Jean-Marie Bruey
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4. Béatrice Eymin
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5. Nathalie Droin
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6. Carmen Garrido
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7. Eric Solary
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Correspondence toEric Solary.

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Edited by K.M. Debatin

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Sordet, O., Bettaieb, A., Bruey, JM. et al. Selective inhibition of apoptosis by TPA-induced differentiation of U937 leukemic cells.Cell Death Differ 6, 351–361 (1999). https://doi.org/10.1038/sj.cdd.4400499

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• Received: 19 August 1998
• Revised: 12 November 1998
• Accepted: 27 January 1999
• Published: 09 April 1999
• Issue Date: 01 April 1999
• DOI: https://doi.org/10.1038/sj.cdd.4400499

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