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Arsenic trioxide-induced apoptosis in U937 cells involve generation of reactive oxygen species and inhibition of Akt

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Author(s)
Yun-Jung ChoiJong-Wook ParkSeong-Il SuhKyo Cheol MunJae Hoon BaeDae-Kyu SongSang-Pyo KimTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg KyuSuh, Seong IlMun, Kyo CheolBae, Jae HoonSong, Dae KyuKim, Sang Pyo
Department
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Dept. of Biochemistry (생화학)
Dept. of Physiology (생리학)
Dept. of Pathology (병리학)
Journal Title
International Journal of Oncology
Issued Date
2002
Volume
21
Issue
3
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. In the present study, we determined the molecular pathways that lead to apoptosis after treatment of cells with arsenic trioxide. Arsenic trioxide treatment of U937 cells leads to apoptosis, which is accompanied by activation of caspase 3 (as measured by decreased levels of the 32 kDa inactive form and increased proteolytic cleavage of PLC-γ1). The broad-range caspase inhibitor z-VAD-fmk inhibits this induction of apoptosis, supporting a direct link between caspase activation and arsenic trioxide induction of apoptosis. This activation of apoptosis is accompanied by release of cytochrome c, down-regulation of cIAP1, and inactivation of Akt. Bcl-2 overexpression attenuates arsenic trioxide-induced apoptosis in U937 cells by inhibition of caspase 3 activity, but not inhibition of Akt. In addition, arsenic trioxide-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant NAC (N-acetyl-cysteine). Co-treatment with NAC markedly prevented dephosphorylation of Akt, activation of caspase 3, and down-regulation of cIAP1. These data indicate that arsenic trioxide can cause cell damage by inactivating the Akt-related cell survival pathway and generating the reactive oxygen species, providing a new mechanism for arsenic trioxide-induced apoptosis.
Keimyung Author(s)(Kor)
박종욱
권택규
서성일
문교철
배재훈
송대규
김상표
Publisher
School of Medicine
Citation
Yun-Jung Choi et al. (2002). Arsenic trioxide-induced apoptosis in U937 cells involve generation of reactive oxygen species and inhibition of Akt. International Journal of Oncology, 21(3), 603–610. doi: 10.3892/ijo.21.3.603
Type
Article
ISSN
1019-6439
Source
https://www.spandidos-publications.com/ijo/21/3/603
DOI
10.3892/ijo.21.3.603
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35926
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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