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[Double effects of arsenic trioxide (As2O3) on acute promyelocytic leukemic cell line]
1Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University.
Objective:
To investigate the effects of a wide range of concentrations of As2O3 on NB4 cells.
Methods:
Cell morphology, cell-DNA content distribution, CD11b and CD33 antigens and nitroblue tetrazolium (NBT) reductions were evaluated in an APL cell line NB4 cells with or without As2O3 treatment. In addition, immunofluorescent analysis for APL marker molecule PML-RAR alpha was also performed.
Results:
1-2 mumol/L of As2O3 treated NB4 cells presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation. Sub-G1 cells, whose percentage presents concentration and time-dependency, were observed by flow cytometer. Otherwise, NB4 cells with the treatment of As2O3 at 0.1-0.25 mumol/L for a long time (10 days) have differentiation-related morphology, and their differentiation antigens CD11b and CD33 were also modulated to some extent. In addition, 0.1-2 mumol/L of As2O3 could rapidly and effectively modulate and degradate PML/PML-RAR alpha proteins.
Conclusion:
As2O3 had double effects (induction of apoptosis and imcomplete differentiation) on NB4 cells, which could associate with rapid modulation and degradation of PML/PML-RAR alpha proteins.