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TY - JOUR AU - Sordet, Olivier AU - Bettaieb, Ali AU - Bruey, Jean-Marie AU - Eymin, Béatrice AU - Droin, Nathalie AU - Ivarsson, Michael AU - Garrido, Carmen AU - Solary, Eric PY - 1999 DA - 1999/04/01 TI - Selective inhibition of apoptosis by TPA-induced differentiation of U937 leukemic cells JO - Cell Death & Differentiation SP - 351 EP - 361 VL - 6 IS - 4 AB - 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. SN - 1476-5403 UR - https://doi.org/10.1038/sj.cdd.4400499 DO - 10.1038/sj.cdd.4400499 ID - Sordet1999 ER -