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Carcinogenesis Advance Access published online on June 29, 2005
Carcinogenesis, doi:10.1093/carcin/bgi167
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received April 7, 2005
Revised June 15, 2005
Accepted June 18, 2005

CANCER BIOLOGY

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

Eun Mi Jung 1 3, Jun Hee Lim 1 3, Tae Jin Lee 1, Jong-Wook Park 1, Kyeong Sook Choi 2, and Taeg Kyu Kwon 1*

1 Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea
2 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.
Taeg Kyu Kwon, E-mail: kwontk{at}dsmc.or.kr


  Abstract

Curcumin exhibits anti-inflammatory and anti-tumor 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 DR5 expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with NAC but also the ectopic expression of peroxiredoxin II (Prx II), an anti-oxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking of curcumin-mediated DR5 up-regulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 up-regulation.

Keywords: TRAIL; Apoptosis; Curcumin; DR5; Reactive Oxygen Species.

3 Both these authors contributed equally to this work


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