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.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by K.M. Debatin
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cdd.4400499
Keywords
This article is cited by
-
Transient delay of radiation-induced apoptosis by phorbol acetate
Radiation and Environmental Biophysics (2016)
-
Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis
Basic Research in Cardiology (2013)
-
L-Glutamic Acid Modulates the Cytotoxic Effect of Tumor Necrosis Factor on the HL-60 Cell Line
Russian Journal of Bioorganic Chemistry (2005)
-
IL-6-independent expression of Mcl-1 in human multiple myeloma
Oncogene (2003)
-
MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis
Leukemia (2002)