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Induction of apoptosis by streptochlorin isolated from Streptomyces sp. in human leukemic U937 cells

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Author(s)
Cheol ParkHee Jae ShinGi-Young KimTaeg Kyu KwonTaek-Jeong NamSe-Kwon KimJaehun CheongIl-Whan ChoiYung Hyun Choi
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Toxicol In Vitro
Issued Date
2008
Volume
22
Issue
6
Keyword
StreptochlorinU937ApoptosisBcl-2Caspase-3
Abstract
Streptochlorin is a small molecule that produced by marine Streptomyces sp. that is known to have anti-
angiogenic and anti-cancer properties. However, the mechanism by which streptochlorin functions is not
well understood. In this study, we investigated the pro-apoptotic effect of streptochlorin in human leu-
kemic U937 cells. Streptochlorin treatment resulted in concentration- and time-dependent growth inhi-
bition by inducing apoptosis. The increase in apoptosis that was induced by streptochlorin was correlated
with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Bax and FasL, a
decrease in the mitochondrial membrane potential (MMP), activation of caspases and degradation of
poly-(ADP-ribose)polymerase and phospholipase C-c1 protein. In addition, the cytotoxic effects and
apoptotic characteristics induced by streptochlorin were significantly inhibited by z-DEVD-fmk, a cas-
pase-3 inhibitor, which demonstrates the important role that caspase-3 played in the process. Further-
more, Bcl-2 overexpression significantly reversed the streptochlorin-induced growth inhibitory effects
via inhibition of the MMP collapse and caspases activation and effectively attenuated the apoptotic
response to streptochlorin. However, the elevated levels of FasL expression induced by streptochlorin
were not reduced by Bcl-2 overexpression. Taken together, these findings demonstrate that the pro-apop-
totic effect of streptochlorin is mediated through activation of caspases and mitochondria in U937 cells.
2008 Elsevier Ltd. All rights reserved. Keywords:
Streptochlorin
U937
Apoptosis
Bcl-2
Caspase-3
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Cheol Park et al. (2008). Induction of apoptosis by streptochlorin isolated from Streptomyces sp. in human leukemic U937 cells. Toxicol In Vitro, 22(6), 1573–1581. doi: 10.1016/j.tiv.2008.06.010
Type
Article
ISSN
0887-2333
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0887233308001677?via%3Dihub
DOI
10.1016/j.tiv.2008.06.010
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34669
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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