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Nuclear Factor κB Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms

Open access
Heiss, Elke, Herhaus, Christian, Klimo, Karin, Bartsch, Helmut, Gerhäuser, Clarissa·2001·Journal of Biological Chemistry

Abstract

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 E(2), 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.

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Research works printed but not linked: 18

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Metadata

Authors
Heiss, E., Herhaus, C., Klimo, K., Bartsch, H., & Gerhäuser, C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-08
Volume
276
Issue
34
Pages
32008-32015
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1991201692
Cited by
632
References
63
FWCI
4.56
Type
journal article
Language
en
Open access
hybrid
Licence

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CoChat. (2026). Citation check: Nuclear Factor κB Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms. https://app.cochat.ai/papers/10.1074/jbc.m104794200
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Heiss, E., Herhaus, C., Klimo, K., Bartsch, H., & Gerhäuser, C. (2001). Nuclear Factor κB Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m104794200

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