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

Heiss, Elke H.; Herhaus, Christian; Klimo, Karin; Bartsch, Helmut; Gerhäuser, Clarissa

doi:10.1074/jbc.m104794200

Cited by 586 publications

(456 citation statements)

References 57 publications

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“…Indeed, increased production of ROS due to HIF inhibition activates NF-B and heightens its role in angiogenesis [38]. that SFN did not block IB/ degradation or nuclear import of the NF-B subunits p50 (NF-B1) and p65 (RelA), but could directly interfere with NF-B DNA binding in vitro [41]. By contrast, others have shown that ITCs reduce phosphorylation and increase expression of IB [42][43][44]46].…”

Section: Hif-independent Control Of Angiogenesismentioning

confidence: 99%

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Cavell

Alwi

Donlevy

et al. 2011

Biochemical Pharmacology

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To cite this version:Breeze E. Cavell, Sharifah S. Syed Alwi, Alison Donlevy, Graham Packham. Anti-angiogenic effects of dietary isothiocyanates; mechanisms of action and implications for human health. Biochemical Pharmacology, Elsevier, 2010, 81 (3) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Isothiocyanates and angiogenesis -3 - AbstractIsothiocyanates (ITCs) are electrophilic compounds derived from plants and are thought to play a major role in the potential chemopreventive effects associated with high intake of cruciferous vegetables. ITCs are also being evaluated for chemotherapeutic activity in early phase clinical trials. In addition to their effects on carcinogen metabolism and cancer cell survival and proliferation, ITCs have been shown to effectively interfere with angiogenesis in vitro and in vivo. Angiogenesis is the development of a new blood supply from existing vasculature and is required for tumours to develop beyond a small size limit determined by the diffusion limit for oxygen. Inhibition of angiogenesis may play a key role in the potential chemopreventive/chemotherapeutic activity of ITCs. In this review we highlight recent data demonstrating that ITCs have anti-angiogenic activity and identify potential molecular targets for these effects, including hypoxia-inducible factor (HIF), nuclear factor B (NF-B), activator protein 1 (AP1) and tubulin. We also discuss these findings in light of the potential chemopreventive/chemotherapeutic effects of ITCs.

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Section: Hif-independent Control Of Angiogenesismentioning

confidence: 99%

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Cavell

Alwi

Donlevy

et al. 2011

Biochemical Pharmacology

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“…NF-kB has been reported to play an important role in several signal transduction pathways involved in various cancers as well as in chronic inflammatory diseases (Rayet and Gelinas, 1999;Bremner and Heinrich, 2002;Aggarwal et al, 2004). SFN was reported to selectively reduce DNA binding of NF-kB without interfering with LPSinduced degradation of the inhibitor of NF-kB nor with nuclear translocation of NF-kB, and NF-kB was identified as the key mediator for sulforaphanemediated anti-inflammatory mechanisms (Heiss et al, 2001). SFN was found to interact with the thiol groups by dithiocarbamate formation, and believed to impair the redox-sensitive DNA binding and transactivation of NF-kB.…”

Section: Introductionmentioning

confidence: 99%

“…SFN was found to interact with the thiol groups by dithiocarbamate formation, and believed to impair the redox-sensitive DNA binding and transactivation of NF-kB. SFN could either directly inactivate NF-kB subunits by binding to essential Cys residues or interact with glutathione or other redox regulators such as thioredoxin and Ref-1 proteins relevant for NF-kB function (Heiss et al, 2001). Human prostate cancer PC-3 cell is an androgen-independent cell line lacking androgen receptor.…”

Section: Introductionmentioning

confidence: 99%

Suppression of NF-κB and NF-κB-regulated gene expression by sulforaphane and PEITC through IκBα, IKK pathway in human prostate cancer PC-3 cells

et al. 2005

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“…Thus, an increased GSH level is essential for carnosol-induced anti-inflammatory effects. Previous studies have demonstrated that changes in the thiol redox state of the cell might affect the posttranslational modification of p65, including the phosphorylation of critical residues shown to contribute to the nuclear import of this molecule [33,34] . Moreover, a recent study has revealed that a number of redox-sensitive transcription factors are modified by GSH and thereby inhibit their function [35] .…”

Section: Discussionmentioning

confidence: 99%

Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival

Chen

Chen²,

Hsieh³

et al. 2010

Acta Pharmacol Sin

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Aim: To explore whether glutathione (GSH) increased through Nrf-2 activation is involved in the cytoprotective effects of carnosol in HepG2 cells. Methods: Human hepatoma cell line HepG2 were exposed to rosemarry essential oil or carnosol. Cell viability was measured using an Alamar blue assay. The production of intracellular GSH was determined using monochlorobimane. The level of protein or mRNA was examined by Western blotting or RT-PCR, respectively. Results: Rosemarry essential oil (0.005%-0.02%) and carnosol (5 and 10 mol/L) increased the intracellular GSH levels and GSH synthesis enzyme subunit GCLC/GCLM expression. Rosemary essential oil and carnosol increased nuclear accumulation of Nrf2 and enhanced Nrf2-antioxidant responsive element (ARE)-reporter activity. Transfection of the treated cells with an Nrf2 siRNA construct blocks GCLC/GCLM induction. Furthermore, pretreatment of the HepG2 cells with essential oil and carnosol exerted significant cytoprotective effects against H 2 O 2 or alcohol. In TNFα-treated cells, the nuclear translocation and transcriptional activity of NF-κB was abolished for 12 h following carnosol pretreatment. Cotreatment with GSH also suppressed NF-κB nuclear translocation, whereas cotreatment with BSO, a GSH synthesis blocker, blocked the inhibitory effects of carnosol. Conclusion: This study demonstrated that Nrf2 is involved in the cytoprotective effects by carnasol, which were at least partially mediated through increased GSH biosynthesis.

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

Cited by 586 publications

References 57 publications

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Suppression of NF-κB and NF-κB-regulated gene expression by sulforaphane and PEITC through IκBα, IKK pathway in human prostate cancer PC-3 cells

Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival

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