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Selective inhibition of apoptosis by TPA-induced differentiation of U937 leukemic cells

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 microM 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 microg/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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https://www.hal.inserm.fr/inserm-02345488
Contributor : Beatrice Eymin <>
Submitted on : Monday, November 4, 2019 - 3:19:09 PM
Last modification on : Friday, September 18, 2020 - 2:34:55 PM

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Olivier Sordet, Ali Bettaieb, Jean-Marie Bruey, Béatrice Eymin, Droin Nathalie, et al.. Selective inhibition of apoptosis by TPA-induced differentiation of U937 leukemic cells. Cell Death and Differentiation, Nature Publishing Group, 1999, 6 (4), pp.351-361. ⟨10.1038/sj.cdd.4400499⟩. ⟨inserm-02345488⟩

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