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Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt

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Author(s)
Ju-Hyung WooYoung-Ho KimYun-Jung ChoDae-Gon KimKyung-Seop LeeJae Hoon BaeDo Sik MinJong-Soo ChangYong-Jin JeongYoung Han LeeJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Bae, Jae HoonPark, Jong WookKwon, Taeg Kyu
Department
Dept. of Physiology (생리학)
Dept. of Immunology (면역학)
Journal Title
Carcinogenesis
Issued Date
2003
Volume
24
Issue
7
Abstract
Curcumin, a natural, biologically active compound
extracted from rhizomes of Curcuma species, has been
shown to possess potent anti-inflammatory, anti-tumor
and anti-oxidative properties. The mechanism by which
curcumin initiates apoptosis remains poorly understood.
In the present report we investigated the effect of curcumin
on the activation of the apoptotic pathway in human renal
Caki cells. Treatment of Caki cells with 50 mM curcumin
resulted in the activation of caspase 3, cleavage of phospholipase
C-g1 and DNA fragmentation. Curcumin-induced
apoptosis is mediated through the activation of caspase,
which is specifically inhibited by the caspase inhibitor,
benzyloxycarbony-Val-Ala-Asp-fluoromethyl ketone. Curcumin
causes dose-dependent apoptosis and DNA fragmentation
of Caki cells, which is preceded by the sequential
dephosphorylation of Akt, down-regulation of the antiapoptotic
Bcl-2, Bcl-XL and IAP proteins, release of cytochrome
c and activation of caspase 3. Cyclosporin A, as
well as caspase inhibitor, specifically inhibit curcumininduced
apoptosis in Caki cells. Pre-treatment with
N-acetyl-cysteine, markedly prevented dephosphorylation
of Akt, and cytochrome c release, and cell death, suggesting
a role for reactive oxygen species in this process. The data
indicate that curcumin can cause cell damage by inactivating
the Akt-related cell survival pathway and release of
cytochrome c, providing a new mechanism for curcumininduced
cytotoxicity.
Keimyung Author(s)(Kor)
배재훈
박종욱
권택규
Publisher
School of Medicine
Citation
Ju-Hyung Woo et al. (2003). Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis, 24(7), 1199–1208. doi: 10.1093/carcin/bgg082
Type
Article
ISSN
0143-3334
DOI
10.1093/carcin/bgg082
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34815
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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