JBC Anatrace, Inc.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M104794200 on June 15, 2001

J. Biol. Chem., Vol. 276, Issue 34, 32008-32015, August 24, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/34/32008    most recent
M104794200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Heiss, E.
Right arrow Articles by Gerhäuser, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heiss, E.
Right arrow Articles by Gerhäuser, C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Nuclear Factor kappa B Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms*

Elke Heiss, Christian Herhaus, Karin Klimo, Helmut Bartsch, and Clarissa GerhäuserDagger

From the Deutsches Krebsforschungszentrum Heidelberg, Division of Toxicology and Cancer Risk Factors, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

Sulforaphane (SFN), an aliphatic isothiocyanate, is a known cancer chemopreventive agent. Aiming to investigate anti-inflammatory mechanisms of SFN, we here report a potent decrease in lipopolysaccharide (LPS)-induced secretion of pro-inflammatory and pro-carcinogenic signaling factors in cultured Raw 264.7 macrophages after SFN treatment, i.e. NO, prostaglandin E2, and tumor necrosis factor alpha . SFN did not directly interact with NO, nor did it inhibit inducible nitric-oxide synthase enzymatic activity. Western blot analyses revealed time- and dose-dependent reduction of LPS-induced inducible nitric-oxide synthase as well as Cox-2 protein expression, which was suppressed at the transcriptional level. To reveal the target of SFN beyond its anti-inflammatory action, we performed electrophoretic mobility shift assay analyses of transcription factor-DNA binding. Consequently, nuclear factor kappa B (NF-kappa B), a pivotal transcription factor in LPS-stimulated pro-inflammatory response, was identified as the key mediator. SFN selectively reduced DNA binding of NF-kappa B without interfering with LPS-induced degradation of the inhibitor of NF-kappa B nor with nuclear translocation of NF-kappa B. Because SFN can interact with thiol groups by dithiocarbamate formation, it may impair the redox-sensitive DNA binding and transactivation of NF-kappa B. Sulforaphane could either directly inactivate NF-kappa B subunits by binding to essential Cys residues or interact with glutathione or other redox regulators like thioredoxin and Ref-1 relevant for NF-kappa B function. Our data provide novel evidence that anti-inflammatory mechanisms contribute to sulforaphane-mediated cancer chemoprevention.

* This work was supported by Verein zur Förderung der Krebsforschung in Deutschland e.V. These data were presented in part at the 90th Annual Meeting of the American Association of Cancer Research, April 10-14, 1999 in Philadelphia, PA (68).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom requests for reprints should be addressed: DKFZ Heidelberg, C0202 Chemoprevention, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Tel.: 49-6221-42-33-06; Fax: 49-6221-42-33-59; E-mail: c.gerhauser@dkfz.de.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
N. G. Innamorato, A. I. Rojo, A. J. Garcia-Yague, M. Yamamoto, M. L. de Ceballos, and A. Cuadrado
The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation
J. Immunol., July 1, 2008; 181(1): 680 - 689.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
G. Pappa, J. Strathmann, M. Lowinger, H. Bartsch, and C. Gerhauser
Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro
Carcinogenesis, July 1, 2007; 28(7): 1471 - 1477.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. V. Gasper, M. Traka, J. R. Bacon, J. A. Smith, M. A. Taylor, C. J. Hawkey, D. A. Barrett, and R. F. Mithen
Consuming Broccoli Does Not Induce Genes Associated with Xenobiotic Metabolism and Cell Cycle Control in Human Gastric Mucosa
J. Nutr., July 1, 2007; 137(7): 1718 - 1724.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Pledgie-Tracy, M. D. Sobolewski, and N. E. Davidson
Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines
Mol. Cancer Ther., March 1, 2007; 6(3): 1013 - 1021.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. M. Yore, K. T. Liby, T. Honda, G. W. Gribble, and M. B. Sporn
The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-{kappa}B activation through direct inhibition of I{kappa}B kinase {beta}
Mol. Cancer Ther., December 1, 2006; 5(12): 3232 - 3239.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. J. Thomson, K. K. Brown, J. M. Pullar, and M. B. Hampton
Phenethyl Isothiocyanate Triggers Apoptosis in Jurkat Cells Made Resistant by the Overexpression of Bcl-2.
Cancer Res., July 1, 2006; 66(13): 6772 - 6777.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. R. Karuri, Y. Huang, S. Bodreddigari, C. H. Sutter, B. D. Roebuck, T. W. Kensler, and T. R. Sutter
3H-1,2-Dithiole-3-thione Targets Nuclear Factor {kappa}B to Block Expression of Inducible Nitric-Oxide Synthase, Prevents Hypotension, and Improves Survival in Endotoxemic Rats
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 61 - 67.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Dey, D. Ribnicky, A. G. Kurmukov, and I. Raskin
In Vitro and in Vivo Anti-Inflammatory Activity of a Seed Preparation Containing Phenethylisothiocyanate
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 326 - 333.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
E. Bertl, H. Bartsch, and C. Gerhauser
Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention.
Mol. Cancer Ther., March 1, 2006; 5(3): 575 - 585.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. Xu, G. Shen, X. Yuan, J.-h. Kim, A. Gopalkrishnan, Y.-S. Keum, S. Nair, and A.-N. T. Kong
ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells
Carcinogenesis, March 1, 2006; 27(3): 437 - 445.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. J. Kwak, J. S. Song, J. Y. Heo, S. D. Yang, J.-Y. Nam, and H. G. Cheon
Roflumilast Inhibits Lipopolysaccharide-Induced Inflammatory Mediators via Suppression of Nuclear Factor-{kappa}B, p38 Mitogen-Activated Protein Kinase, and c-Jun NH2-Terminal Kinase Activation
J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1188 - 1195.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Dasgupta, M. Jana, X. Liu, and K. Pahan
Myelin Basic Protein-primed T Cells of Female but Not Male Mice Induce Nitric-oxide Synthase and Proinflammatory Cytokines in Microglia: IMPLICATIONS FOR GENDER BIAS IN MULTIPLE SCLEROSIS
J. Biol. Chem., September 23, 2005; 280(38): 32609 - 32617.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. T. Dinkova-Kostova, K. T. Liby, K. K. Stephenson, W. D. Holtzclaw, X. Gao, N. Suh, C. Williams, R. Risingsong, T. Honda, G. W. Gribble, et al.
Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress
PNAS, March 22, 2005; 102(12): 4584 - 4589.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Kumagai, N. Matsukawa, Y. Kaneko, Y. Kusumi, M. Mitsumata, and K. Uchida
A Lipid Peroxidation-derived Inflammatory Mediator: IDENTIFICATION OF 4-HYDROXY-2-NONENAL AS A POTENTIAL INDUCER OF CYCLOOXYGENASE-2 IN MACROPHAGES
J. Biol. Chem., November 12, 2004; 279(46): 48389 - 48396.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N.-A. Pham, J. W. Jacobberger, A. D. Schimmer, P. Cao, M. Gronda, and D. W. Hedley
The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice
Mol. Cancer Ther., October 1, 2004; 3(10): 1239 - 1248.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
V. Svehlikova, S. Wang, J. Jakubikova, G. Williamson, R. Mithen, and Y. Bao
Interactions between sulforaphane and apigenin in the induction of UGT1A1 and GSTA1 in CaCo-2 cells
Carcinogenesis, September 1, 2004; 25(9): 1629 - 1637.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B.-C. Chen, Y.-S. Chang, J.-C. Kang, M.-J. Hsu, J.-R. Sheu, T.-L. Chen, C.-M. Teng, and C.-H. Lin
Peptidoglycan Induces Nuclear Factor-{kappa}B Activation and Cyclooxygenase-2 Expression via Ras, Raf-1, and ERK in RAW 264.7 Macrophages
J. Biol. Chem., May 14, 2004; 279(20): 20889 - 20897.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
N. Miyoshi, S. Takabayashi, T. Osawa, and Y. Nakamura
Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: implication for prevention against inflammation-related carcinogenesis
Carcinogenesis, April 1, 2004; 25(4): 567 - 575.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Dasgupta, M. Jana, X. Liu, and K. Pahan
Role of Very-late Antigen-4 (VLA-4) in Myelin Basic Protein-primed T Cell Contact-induced Expression of Proinflammatory Cytokines in Microglial Cells
J. Biol. Chem., June 13, 2003; 278(25): 22424 - 22431.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
L. M. Howells, B. Gallacher-Horley, C. E. Houghton, M. M. Manson, and E. A. Hudson
Indole-3-carbinol Inhibits Protein Kinase B/Akt and Induces Apoptosis in the Human Breast Tumor Cell Line MDA MB468 but not in the Nontumorigenic HBL100 Line
Mol. Cancer Ther., November 1, 2002; 1(13): 1161 - 1172.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. Gerhauser, A. Alt, E. Heiss, A. Gamal-Eldeen, K. Klimo, J. Knauft, I. Neumann, H.-R. Scherf, N. Frank, H. Bartsch, et al.
Cancer Chemopreventive Activity of Xanthohumol, a Natural Product Derived from Hop
Mol. Cancer Ther., September 1, 2002; 1(11): 959 - 969.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
G. P. Basten, Y. Bao, and G. Williamson
Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells
Carcinogenesis, August 1, 2002; 23(8): 1399 - 1404.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.