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

Authors
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
Department
Dept. of Physiology (생리학); Dept. of Immunology (면역학)
Issue Date
2003
Citation
Carcinogenesis, Vol.24(7) : 1199-1208, 2003
ISSN
0143-3334
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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34815
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
Keimyung Author(s)
배재훈; 박종욱; 권택규
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