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Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion

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Author(s)
Byeong-Churl JangJong-Gu ParkDae-Kyu SongWon-Ki BaekSun Kyun YooKyung-Hwan JungGy-Young ParkTae-Yun LeeSeong-Il Suh
Keimyung Author(s)
Jang, Byeong ChurlPark, Jong GuSong, Dae KyuBaek, Won KiSuh, Seong Il
Department
Dept. of Molecular Medicine (분자의학)
Dept. of Physiology (생리학)
Dept. of Microbiology (미생물학)
Journal Title
Toxicol In Vitro
Issued Date
2009
Volume
23
Issue
2
Keyword
SanguinarineApoptosisGlutathione depletionCaspasesA549 cells
Abstract
Sanguinarine is a plant-derived benzophenanthridine alkaloid and has been shown to possess anti-tumor
activities against various cancer cells. In this study, we investigated whether sanguinarine induces apop-
tosis in A549 human lung cancer cells. Treatment of A549 cells with sanguinarine induced apoptosis in a
dose- and time-dependent manner. Treatment with sanguinarine led to activation of caspases and MAPKs
as well as increased MKP-1 expression. Importantly, pretreatment with z-VAD-fmk, a pan caspase inhib-
itor suppressed the sanguinarine-induced apoptosis in A549 cells. Moreover, pretreatment with NAC, a
sulfhydryl group-containing reducing agent strongly suppressed the apoptotic response and caspase acti-
vation to sanguinarine. However, the sanguinarine-mediated cytotoxicity in A549 cells was not protected
by pharmacological inhibition of MAPKs or MKP-1 siRNA-mediated knockdown of MKP-1. These results
collectively suggest that sanguinarine induces apoptosis in A549 cells through cellular glutathione deple-
tion and the subsequent caspase activation.
2008 Elsevier Ltd. All rights reserved. Keywords:
Sanguinarine
Apoptosis
Glutathione depletion
Caspases
A549 cells
Keimyung Author(s)(Kor)
장병철
박종구
송대규
백원기
서성일
Publisher
School of Medicine
Citation
Byeong-Churl Jang et al. (2009). Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion. Toxicol In Vitro, 23(2), 281~287-281~287. doi: 10.1016/j.tiv.2008.12.013
Type
Article
ISSN
0887-2333
Source
http://lps3.linkinghub.elsevier.com.proxy.dsmc.or.kr/retrieve/pii/S0887-2333(08)00294-4
DOI
10.1016/j.tiv.2008.12.013
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34673
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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