Carcinogenesis Advance Access published online on May 9, 2003
Carcinogenesis, doi:10.1093/carcin/bgg082
© 2003 by Oxford University Press
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CANCER BIOLOGY
1 Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, 700-712, South Korea
* Corresponding author. E-mail: kwontk{at}dsmc.or.kr.
Received 17 December 2002
; revised 25 April 2003
; accepted 28 April 2003
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 µM curcumin resulted in the activation of caspase 3, cleavage of PLC-
Curcumin, Reactive Oxygen Species, Caki cells, Apoptosis, Caspase 3, Cytochrome c
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
2 Department of Urology, College of Medicine, Dongguk University, Kyungju, South Korea
3 Department of Physiology School of Medicine, Keimyung University, Taegu, South Korea
4 Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea
5 Department of Life Science, Daejin University, Pochon-gun, Kyeonggido, South Korea
6 Department of Food Science and Technology, Keimyung University, Taegu, South Korea
7 Department of Biochemistry, College of Medicine, Yeungnam University, Taegu, South Korea
1 and DNA fragmentation. Curcumin-induced apoptosis is mediated through the activation of caspase, which is specifically inhibited by the caspase inhibitor, z-VAD-fmk. Curcumin causes dose-dependent apoptosis and DNA fragmentation of Caki cells, which is preceded by the sequential dephosphorylation of Akt, down-regulation of the anti-apoptotic 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 curcumin-induced apoptosis in Caki cells. Pretreatment with NAC (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. These 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 curcumin-induced cytotoxicity.
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