Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro
IS Kim, JY Jin, IH Lee, SJ Park - British journal of pharmacology, 2004 - Wiley Online Library
IS Kim, JY Jin, IH Lee, SJ Park
British journal of pharmacology, 2004•Wiley Online LibraryAcute promyelocytic leukaemia (APL) is characterized by a block in differentiation at the
promyelocyte stage. Here, we describe the effects of auranofin (AF), a coordinated gold
compound, on apoptosis and differentiation of APL cells. Nucleosomal DNA fragmentation
assay and Hoechst 33342 staining indicated that AF induced apoptosis in APL‐derived NB4
cells at low concentrations (0.5–1.0 μm). The AF‐induced apoptosis involved caspase‐3
activation and specific cleavage of poly‐ADP‐ribose polymerase. The AF‐treated NB4 cells …
promyelocyte stage. Here, we describe the effects of auranofin (AF), a coordinated gold
compound, on apoptosis and differentiation of APL cells. Nucleosomal DNA fragmentation
assay and Hoechst 33342 staining indicated that AF induced apoptosis in APL‐derived NB4
cells at low concentrations (0.5–1.0 μm). The AF‐induced apoptosis involved caspase‐3
activation and specific cleavage of poly‐ADP‐ribose polymerase. The AF‐treated NB4 cells …
- Acute promyelocytic leukaemia (APL) is characterized by a block in differentiation at the promyelocyte stage. Here, we describe the effects of auranofin (AF), a coordinated gold compound, on apoptosis and differentiation of APL cells.
- Nucleosomal DNA fragmentation assay and Hoechst 33342 staining indicated that AF induced apoptosis in APL‐derived NB4 cells at low concentrations (0.5–1.0 μM). The AF‐induced apoptosis involved caspase‐3 activation and specific cleavage of poly‐ADP‐ribose polymerase.
- The AF‐treated NB4 cells also produced reactive oxygen species (ROS) and cotreatment with N‐acetyl‐L‐cysteine protected the NB4 cells from AF‐induced apoptosis.
- Expression of the CD11b cell surface marker and C/EBPɛ was increased when the cells were treated for 4 days with 0.3 μM AF and a physiological concentration of all‐trans retinoic acid (ATRA, 5 nM). Treatment with AF in combination with ATRA markedly increased the number of cells with differentiated features, such as lobed or multiple nuclei and numerous granules and vacuoles. At these low concentrations, neither AF nor ATRA alone induced significant cell differentiation.
- These findings suggest not only that AF induces caspase‐3‐dependent apoptosis via a mechanism involving ROS, but also that the combined treatment with AF and ATRA induces differentiation of NB4 cells. Our results demonstrate a novel characteristic of AF from which an effective drug treatment of APL might be developed.
British Journal of Pharmacology (2004) 142, 749–755. doi:10.1038/sj.bjp.0705708
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