Modulatory Properties of Various Natural Chemopreventive Agents on the Activation of NF-κB Signaling Pathway

Jeong, Woo-Sik; Kim, In‐Wha; Hu, Rong; Kong, Ah‐Ng Tony

doi:10.1023/b:pham.0000022413.43212.cf

Cited by 258 publications

(161 citation statements)

References 43 publications

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“…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]. SFN and PEITC inhibited IKK-mediated phosphorylation of IB in an in vitro assay, suggesting that IKK may be a direct target for modulation by ITCs [44].…”

Section: Hif-independent Control Of Angiogenesismentioning

confidence: 92%

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: 92%

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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“…The most common nuclear factor kappa B (NF-kB) is a heterodimer composed of p65 and p50 (Greten and Karin, 2004;Suh and Rabson, 2004). NF-kB is activated by a wide variety of stimuli such as tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), LPS, UV light, and oxidative stress (Jeong et al, 2004;Takada et al, 2004b). In most cell types, NF-kB is present in the cytosol in an inactive form and is associated with its inhibitor proteins, called inhibitor of NF-kB (IkBs).…”

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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“…The major mechanism of sulforaphane action was inhibition of nuclear factor-nB (NF-nB) binding to DNA presumably through modulation of intracellular redox conditions via dithiocarbamoylation of essential thiol groups involved in the activation of NF-nB. Sulforaphane-mediated inhibition of LPS-induced NF-nB-mediated transactivation was recently confirmed in HT-29 cells stably transfected with NF-nB luciferase constructs (16). (d) In addition, sulforaphane possesses antiproliferative and apoptosis-inducing properties as shown in various cancer cell lines and in vivo (17,18).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention

Bertl

Bartsch

Gerhäuser

2006

Molecular Cancer Therapeutics

166

124

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Sulforaphane, an aliphatic isothiocyanate, is a known cancer chemopreventive agent. Aiming to investigate antiangiogenic potential of sulforaphane, we here report a potent decrease of newly formed microcapillaries in a human in vitro antiangiogenesis model, with an IC 50 of 0.08 Mmol/L. The effects of sulforaphane on endothelial cell functions essential for angiogenesis were investigated in HMEC-1, an immortalized human microvascular endothelial cell line. Molecular signaling pathways leading to activation of endothelial cell proliferation and degradation of the basement membrane were analyzed by reverse transcription-PCR. Sulforaphane showed time-and concentration-dependent inhibitory effects on hypoxiainduced mRNA expression of vascular endothelial growth factor and two angiogenesis-associated transcription factors, hypoxia-inducible factor-1A and c-Myc, in a concentration range of 0.8 to 25 Mmol/L. In addition, the expression of the vascular endothelial growth factor receptor KDR/flk-1 was inhibited by sulforaphane at the transcriptional level. Sulforaphane could also affect basement membrane integrity, as it suppressed transcription of the predominant endothelial collagenase matrix metalloproteinase-2 and its tissue inhibitor of metalloproteinase-2. Migration of HMEC-1 cells in a wound healing assay was effectively prevented by sulforaphane at submicromolar concentrations, and we determined an IC 50 of 0.69 Mmol/L. In addition, within 6 hours of incubation, sulforaphane inhibited tube formation of HMEC-1 cells on basement membrane matrix at 0.1, 1, and 10 Mmol/L concentrations. These effects were not due to inhibition of HMEC-1 cell proliferation; however, after 72 hours of incubation, sulforaphane nonselectively reduced HMEC-1 cell growth with an IC 50 of 11.3 Mmol/L. In conclusion, we have shown that sulforaphane interferes with all essential steps of neovascularization from proangiogenic signaling and basement membrane integrity to endothelial cell proliferation, migration, and tube formation. These novel antiangiogenic activities of sulforaphane are likely to contribute to its cancer chemopreventive and therapeutic potential. [Mol Cancer Ther 2006;5(3):575 -85]

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Modulatory Properties of Various Natural Chemopreventive Agents on the Activation of NF-κB Signaling Pathway

Abstract: These results suggest that natural chemopreventive agents have differential biological functions on the signal transduction pathways in the colon and/or colon cancer.

Cited by 258 publications

References 43 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

Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention

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