Carcinogenesis Advance Access first published online on April 12, 2006
This version published online on April 13, 2006
Carcinogenesis, doi:10.1093/carcin/bgl026
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1 Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea
* To whom correspondence should be addressed. Death receptor DR5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we showed that curcumin, a plant product containing the phenolic phytochemical, is a potent enhancer of TRAIL-induced apoptosis through up-regulation of DR5 expression. Both treatment with DR5/Fc chimeric protein and silencing of DR5 expression using small interfering RNA (siRNA) attenuated curcumin plus TRAIL-induced apoptosis, showing that the critical role of DR5 in this cell death. Curcumin also induced the expression of a potential pro-apoptotic gene, C/EBP homologous protein (CHOP), both at its mRNA and protein levels. However, suppression of CHOP expression by small interfering RNA did not abrogate the curcumin-mediated induction of DR5 and the cell death induced by curcumin plus TRAIL, demonstrating that CHOP is not involved in curcumin-induced DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by CHOP-independent upregulation of DR5.
Received November 15, 2005
Revised March 7, 2006
Accepted March 19, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation
Eun Mi Jung 1,
Jong-Wook Park 1,
Kyeong Sook Choi 2,
Jeen-Woo Park 3,
Hyung I. L. Lee 4,
Kyung-Seop Lee 4,
and
Taeg Kyu Kwon 1 *
2 Institute for Medical Sciences, Ajou University School of Medicine, 5 Woncheon-Dong, Paldal-Gu, Suwon 442-749, South Korea
3 School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea
4 Department of Urology, College of Medicine, Dongguk University, Kyungju, South Korea
Taeg Kyu Kwon, E-mail: kwontk{at}dsmc.or.kr
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