Carcinogenesis Advance Access published online on March 29, 2006
Carcinogenesis, doi:10.1093/carcin/bgl015
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
* To whom correspondence should be addressed. Sulforaphane (SFN), a naturally occurring isothiocyanate, is an attractive agent due to its potent anticancer effects. SFN suppresses the proliferation of various cancer cells in vitro and in vivo. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is also one of the most promising candidates for cancer therapeutics due to its ability to selectively induce apoptosis in tumor cells. In this study, we report that SFN enhances TRAIL-induced apoptosis in human osteosarcoma cells, Saos2 and MG63. The apoptosis induced by co-treatment with SFN and TRAIL was markedly blocked by a dominant negative form of the TRAIL receptor or caspase inhibitors. The combined use of SFN and TRAIL effectively induced Bid cleavage and the activation of caspase-8, -10, -9 and -3 at ineffective concentrations for each agent. SFN up-regulated the expression of death receptor 5 (DR5), a receptor for TRAIL, at mRNA and protein levels in a dose-dependent manner. In addition, the SFN-mediated sensitization to TRAIL was reduced by DR5 siRNA, suggesting that the sensitization was at least partially mediated through the induction of DR5 expression. Furthermore, SFN sensitized TRAIL-induced apoptosis in a p53-independent manner. On the other hand, SFN neither induced DR5 protein expression or enhanced TRAIL-induced apoptosis in normal human peripheral blood mononuclear cells. Thus, combined treatment with SFN and TRAIL might be a promising therapy for osteosarcoma.
Received December 21, 2005
Revised March 13, 2006
Accepted March 15, 2006
CANCER BIOLOGY
Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells
Taka-aki Matsui 1,
Yoshihiro Sowa 2,
Tatsushi Yoshida 2,
Hiroaki Murata 3,
Mano Horinaka 2,
Miki Wakada 2,
Ryoko Nakanishi 2,
Tomoya Sakabe 3,
Toshikazu Kubo 3,
and
Toshiyuki Sakai 2 *
2 Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
3 Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Toshiyuki Sakai, E-mail: tsakai{at}koto.kpu-m.ac.jp
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.-J. Chen, C.-W. Chou, Y.-F. Chang, and C.-C. Chen Proteasome Inhibitors Enhance TRAIL-Induced Apoptosis through the Intronic Regulation of DR5: Involvement of NF-{kappa}B and Reactive Oxygen Species-Mediated p53 Activation J. Immunol., June 15, 2008; 180(12): 8030 - 8039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Locklin, E. Federici, B. Espina, P. A. Hulley, R. G. G. Russell, and C. M. Edwards Selective targeting of death receptor 5 circumvents resistance of MG-63 osteosarcoma cells to TRAIL-induced apoptosis Mol. Cancer Ther., December 1, 2007; 6(12): 3219 - 3228. [Abstract] [Full Text] [PDF]
|
|