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

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, Taeg Kyu Kwon

Research output: Contribution to journalArticle

322 Citations (Scopus)

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 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 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 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.

Original languageEnglish
Pages (from-to)1199-1208
Number of pages10
JournalCarcinogenesis
Volume24
Issue number7
DOIs
Publication statusPublished - 2003 Jul 1

All Science Journal Classification (ASJC) codes

  • Cancer Research

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