title: Modulation of death receptor-mediated apoptosis in differentiating human myeloid leukemia HL-60 cells.
abstract: Differentiating myeloid cells may become resistant to various apoptotic stimuli. In the present study, dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA) were found to modulate the sensitivity of HL-60 cells to death receptor-mediated apoptosis in a time-dependent manner. During the early stages of differentiation, DMSO treatment increased the response of HL-60 cells to tumor necrosis factor alpha; (TNF-alpha), but enhanced responsiveness was lost during later differentiation stages. In contrast, ATRA treatment induced resistance to TNF-alpha-induced apoptosis. HL-60 cells were resistant to Fas-mediated apoptosis but were sensitized by culturing in serum-free conditions. Similar to its effect on TNF-alpha sensitivity, DMSO pretreatment augmented the response to Fas-mediated signaling, which coincided with increased expression of Fas on DMSO-pretreated cells. However, during the later stages of DMSO-induced differentiation, sensitivity to anti-Fas antibody-induced apoptosis declined significantly, although Fas expression was still elevated. The reduced sensitivity to anti-Fas treatment partially correlated with increased Fas-associated phosphatase-1 mRNA expression. Thus, regardless of either Fas up-regulation or potentiation of TNF-alpha-mediated apoptosis during early DMSO-induced differentiation, a slow increase in resistance to apoptosis mediated through these death receptors occurs during DMSO-induced differentiation, which contrasts with the rapid induction of resistance following treatment with ATRA.
authors.affiliation: Institute of Biophysics, Mendel University, Brno, Czech Republic. hivrisik@ibp.cz
authors.forename: J
authors.initials: J
authors.lastname: Vondrácek
authors.forename: M A
authors.initials: MA
authors.lastname: Sheard
authors.forename: P
authors.initials: P
authors.lastname: Krejcí
authors.forename: K
authors.initials: K
authors.lastname: Minksová
authors.forename: J
authors.initials: J
authors.lastname: Hofmanová
authors.forename: A
authors.initials: A
authors.lastname: Kozubík
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D016895:Culture Media, Serum-Free; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D047889:Receptors, Tumor Necrosis Factor, Type II; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D014212:Tretinoin; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; D004121:Dimethyl Sulfoxide