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Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells

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Author(s)
Tae-Jin LeeEun Jung KimShin KimEun Mi JungJong-Wook ParkSeung Hun JeongSang Eun ParkYoung Hyun YooTaeg Kyu Kwon
Keimyung Author(s)
Kim, ShinPark, Jong WookKwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Institute for Medical Science (의과학연구소)
Journal Title
Molecular Cancer Therapeutics
Issued Date
2006
Volume
5
Issue
9
Abstract
Evodiamine is one of the major bioactive compounds that
have been isolated and purified from the fruit of Evodiae
fructus. Evodiamine exhibits antitumor activities against
the human tumor cells, including multidrug-resistant tumor
cells. However, the molecular mechanism involved in cell
death induced by evodiamine treatment remains poorly
understood. In the present study, we showed that evodiamine
activated the caspase-dependent apoptotic pathway.
This apoptosis was only partially inhibited by a
pancaspase inhibitor benzyloxycarbonyl-Val-Ala-Aspfluoromethyl
ketone, which suggested that evodiamineinduced
apoptosis in leukemic U937 cells is partially
caspase independent. We observed the nuclear translocation
of apoptosis-inducing factor in evodiamine-induced
apoptosis of U937 cells, which may be responsible for
the caspase-independent apoptotic execution. We next
showed that evodiamine induced the substantial amount
of apoptosis both in Bcl-2- and Akt-overexpressing U937
cells but not in human peripheral blood mononuclear cells.
Although benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl
ketone inhibited caspase activity in Bcl-2-overexpressing
U937 cells, it completely prevented neither the induction
of apoptosis or the nuclear translocation of apoptosisinducing
factor, which suggests that evodiamine is, at
least in part, able to bypass the resistance of leukemia cells
via caspase-independent apoptotic pathways. Thus, therapeutic
strategy using evodiamine may warrant further
evaluation. [Mol Cancer Ther 2006;5(9):2398–407]
Keimyung Author(s)(Kor)
김신
박종욱
권택규
Publisher
School of Medicine
Citation
Tae-Jin Lee et al. (2006). Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells. Molecular Cancer Therapeutics, 5(9), 2398–2407. doi: 10.1158/1535-7163.MCT-06-0167
Type
Article
ISSN
1535-7163
DOI
10.1158/1535-7163.MCT-06-0167
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33436
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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