Journal Article

Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-X<sub>L</sub> and IAP, the release of cytochrome <i>c</i> and inhibition of Akt

Ju-Hyung Woo, Young-Ho Kim, Yun-Jung Choi, Dae-Gon Kim, Kyung-Seop Lee, Jae Hoon Bae, Do Sik Min, Jong-Soo Chang, Yong-Jin Jeong, Young Han Lee, Jong-Wook Park and Taeg Kyu Kwon

in Carcinogenesis

Volume 24, issue 7, pages 1199-1208
Published in print July 2003 | ISSN: 0143-3334
Published online July 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg082
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

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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 phospholipase C-γ1 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 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. 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 curcumin-induced cytotoxicity.

Keywords: DEVD-pNA, Asp-Glu-Val-Asp-chromophore p-nitroanilide; H2DCFDA, 2,7-dichlorodihydrofluorescein diacetate; NAC, N-acetyl-cysteine; PLC-γ1, phospholipase C-γ1; ROS, reactive oxygen species; z-VAD-fmk, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone

Journal Article.  6554 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.