Journal Article

Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5)

Eun Mi Jung, Jun Hee Lim, Tae Jin Lee, Jong-Wook Park, Kyeong Sook Choi and Taeg Kyu Kwon

in Carcinogenesis

Volume 26, issue 11, pages 1905-1913
Published in print November 2005 | ISSN: 0143-3334
Published online June 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi167
Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5)

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Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.

Keywords: DMEM, Dulbecco's modified Eagle's medium; DR5, death receptor 5; FACS, fluorescent activated cell sorting; FCS, fetal calf serum; FITC, fluorescein isothiocyanate; FLIP, Flice-inhibitory protein; NAC, N-acetylcystine; Prx II, peroxiredoxin II; ROS, reactive oxygen species; RT–PCR, reverse transcriptase–polymerase chain reaction; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand

Journal Article.  6139 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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