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Failure to activate caspase 3 in phorbol ester-resistant leukemia cells is associated with resistance to apoptotic cell death

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Author(s)
Yun-Jung ChoiJong-Wook ParkJu-Hyung WooYoung-Ho KimSang-Han LeeJin-Man LeeTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Cancer Letters
Issued Date
2002
Volume
182
Issue
2
Abstract
The protein kinase C (PKC)-specific inhibitor, Ro-31-8220, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. In the present study, we determined the molecular pathways that lead to apoptosis after treatment of cells with the PKC-specific inhibitor RO-31-8220. For this, we used the U937 human leukemia cell line and a phorbolmyristate acetate (PMA)-resistant derivative cell line, R-U937. Ro-31-8220 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 phospholipase C (PLC)-γ1). The broad-range caspase inhibitor z-VAD-fmk inhibits this induction of apoptosis, supporting a direct link between caspase activation and Ro-31-8220 induction of apoptosis. This activation of apoptosis is also accompanied by release of cytochrome c, but not by altered expression of Bcl-2 family protein or IAP family proteins. In R-U937 cells, Ro-31-8220 fails to cause release of cytochrome c, activation of caspase 3, or apoptosis. Activation of Akt occurs to a greater extent in the R-U937 cells than the U937 cells and thus might be related to protection from Ro-31-8220-induced apoptosis.

Keywords
Protein kinase C inhibitor;
Cell cycle;
Apoptosis;
Caspase 3;
Akt
Keimyung Author(s)(Kor)
박종욱
권택규
Publisher
School of Medicine
Citation
Yun-Jung Choi et al. (2002). Failure to activate caspase 3 in phorbol ester-resistant leukemia cells is associated with resistance to apoptotic cell death. Cancer Letters, 182(2), 183–191. doi: 10.1016/S0304-3835(02)00082-4
Type
Article
ISSN
0304-3835
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0304383502000824?via%3Dihub
DOI
10.1016/S0304-3835(02)00082-4
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35316
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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