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Arsenic Trioxide Induces G2/M Growth Arrest and Apoptosis after Caspase-3 Activation and Bcl-2 Phosphorylation in Promonocytic U937 Cells

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Author(s)
Jong-Wook ParkYun-Jung ChoiMin Ah JangSuk-Hwan BaekJun Hee LimTony PassanitiTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Biochemical and Biophysical Research Communications
Issued Date
2001
Volume
286
Issue
4
Abstract
Arsenic trioxide has recently been shown to inhibit growth and induce apoptosis in acute promyelocytic leukemia (APL), but little is known about the molecular mechanisms mediating these effects. Here we demonstrate that treatment of promonocytic U937 cells with arsenic trioxide leads to G2/M arrest which was associated with a dramatic increase in the levels of cyclin B and cyclin B-dependent kinase and apoptosis. We further show that apoptosis occurs after bcl-2 phosphorylation and caspase-3 activation followed by cleavage of PARP and PLC-γ1 degradation and DNA fragmentation. The arsenic trioxide-induced apoptosis could be blocked by the protein synthesis inhibitor cycloheximide. In addition, pretreatment of U937 cells with the DNA polymerase inhibitor aphidicolin also blocked apoptosis, but did not cause the arrest of cells in the G2/M phase. The findings suggest that arsenic trioxide exerts its growth-inhibitory effects by modulating expression and/or activity of several key G2/M regulatory proteins. Furthermore, arsenic trioxide-mediated G2/M arrest correlates with the onset of apoptosis.

Keywords
arsenic trioxide;
apoptosis;
bcl-2 phosphorylation;
cell cycle;
leukemia
Keimyung Author(s)(Kor)
박종욱
권택규
Publisher
School of Medicine
Citation
Jong-Wook Park et al. (2001). Arsenic Trioxide Induces G2/M Growth Arrest and
Apoptosis after Caspase-3 Activation and Bcl-2
Phosphorylation in Promonocytic U937 Cells. Biochemical and Biophysical Research Communications, 286(4), 726–734. doi: 10.1006/bbrc.2001.5416
Type
Article
ISSN
0006-291X
Source
https://linkinghub.elsevier.com/retrieve/pii/S0006291X01954166
DOI
10.1006/bbrc.2001.5416
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35181
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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