Carcinogenesis Advance Access originally published online on June 29, 2005
Carcinogenesis 2005 26(11):1905-1913; doi:10.1093/carcin/bgi167
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Carcinogenesis vol.26 no.11 © Oxford University Press 2005; all rights reserved.
Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5)
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea and 1 Institute for Medical Sciences, Ajou University School of Medicine, 5 Woncheon-Dong, Paldal-Gu, Suwon 442-749, South Korea
* To whom correspondence should be addressed. Tel: +82 53 250 7846; Fax: +82 53 250 7074; Email: kwontk{at}dsmc.or.kr
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.
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