Is NF-κB a good target for cancer therapy? Hopes and pitfalls

Baud, Véronique; Karin, Michael

doi:10.1038/nrd2781

Cited by 972 publications

(915 citation statements)

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“…The molecular mechanisms underling this process have only recently started to be clarified with biochemical and genetic studies (95). The results of Pikarsky et al (8) , Greten et al (72) , and Luo et al (78) identified the NF-B signaling pathway could be regarded as a rational target for cancer therapy, and there is significant enthusiasm from cell culture experiments and animal models for the use of NF-B inhibitors as a new anti-cancer therapy in recent years (14,96,97). However, several questions remain.…”

Section: Discussionmentioning

confidence: 99%

“…The pivotal role of the NF-B signaling pathway in apoptosis, tumor promotion and tumor maintenance, strongly suggests that NF-B inhibitors would be useful in cancer therapy, and much efforts is currently invested in developing NF-B inhibitors in cancers (10,14,85,86). Several agents have been implemented to inhibit IKK/NF-B activity, because of the relevance of this process in cancer and those related with inflammation, such as curcumin, ginseng extract, resveratrol, green tea extract have anti-inflammatory and antiproliferative propertiese (87).…”

Section: Nf-b Inhibition: Strategy For Colorectal Cancer Therapymentioning

confidence: 99%

“…The detailed description of NF-B structure, function and regulation is beyond the scope of this review (see recent review (14)(15)(16)). Briefly, five homologous subunits have been identified in mammals: RelA/p65, c-Rel, RelB, NF-B1/p50, and NF-B2/p52.…”

Section: Introductionmentioning

confidence: 99%

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NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

et al. 2009

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There is growing evidence for a connection between inflammation and tumor development, and the nuclear factor kappa B (NF-B), a proinflammatory transcription factor, is hypothesized to promote tumorigenesis. Although the genetic evidence for the hypothesis has been lacking, recent papers have lent credence to this hypothesis. It has been reported that constitutive NF-B activation in inflammatory bowel diseases (

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Section: Discussionmentioning

confidence: 99%

Section: Nf-b Inhibition: Strategy For Colorectal Cancer Therapymentioning

confidence: 99%

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NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

et al. 2009

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“…While normal activation of NF-B is required for cell survival and immunity, it is now well established that the deregulated activation of NF-B is associated with cancer, inflammation, and a wide range of other pathologies [3][4][5][6][7][8][9][10][11]. Because of its severe implications in a large number of diseases, NF-B has recently become a major target in drug discovery [4,7,8,12].…”

Section: Introductionmentioning

confidence: 99%

The inhibition of TNF-α-induced NF-κB activation by marine natural products

Folmer

Jaspars

Solano

et al. 2009

Biochemical Pharmacology

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, et al.. The inhibition of TNF-α induced NF-κB activation by marine natural products. Biochemical Pharmacology, Elsevier, 2009, 78 (6) 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 AbstractThe deregulated activation of NF-B is associated with cancer development and inflammatory diseases. With the aim to find new NF-B inhibitors, we purified and characterized compounds from extracts of the Fijian sponge Rhabdastrella globostellata, the crinoid Comanthus parvicirrus, the soft corals Sarcophyton sp. nov. and Sinularia sp., and the gorgonian Subergorgia sp. after an initial screening of 266 extracts from different marine origins.Results obtained show that selected purified compounds had a cytotoxic effect on the human leukaemia cell line K562, inhibited both TNF--induced NF-B-DNA binding as well as TNF- induced IB degradation and nuclear translocation of p50/p65. Furthermore, we observed inhibition of NF-B activation induced by an overexpression of TNFR1, TRAF2, TRADD, or IKK Interestingly, natural products inhibited IKK kinase as well as the 26S proteasome proteolytic activity.

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“…Activation of NF-jB promotes transcription of a wide variety of genes, which are related to inflammation and tumor growth (Baud and Karin 2009). Many studies have shown that NF-jB plays a crucial role in the pathogenesis of esophageal adenocarcinoma (Abdel-Latif et al 2004;Konturek et al 2004;O'Riordan et al 2005).…”

Section: Gsk3b Affects Tumorigenesis Of Ec Through Transcription Factmentioning

confidence: 99%

The Role of Glycogen Synthase Kinase 3-β in Immunity and Cell Cycle: Implications in Esophageal Cancer

Gao

Brown

Wang

et al. 2013

Arch. Immunol. Ther. Exp.

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Esophageal cancer (EC) is one of the most aggressive gastrointestinal malignancies, possessing an insidious onset and a poor prognosis. Numerous transcription factors and inflammatory mediators have been reported to play a pivotal role in the initiation and progression of this cancer. However, the specifics of the signaling network responsible for said factors, especially which elements are the critical regulators, are still being elucidated. Glycogen synthesis kinases 3 (GSK3)b was originally regarded as a kinase regulating glucose metabolism. Accumulating evidence demonstrated that it also played an essential role in a variety of cellular processes including proliferation, differentiation, inflammation, motility, and survival by regulating various transcription factors such as c-Jun, AP-1, b-catenin, CREB, and NF-jB. Aberrant regulation of GSK3b has been shown to promote cell growth in some cancers, while suppressing it in others, and thus may play an important role in the development of EC. This review will discuss our current understanding of GSK3b signaling, and its control of the expression and activation of various transcription factors that mediate the inflammatory response. We will also explore some of the known mediators of EC progression, and based on current literature, elucidate the potential roles and implications of GSK3 in this disease.

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Is NF-κB a good target for cancer therapy? Hopes and pitfalls

Cited by 972 publications

References 102 publications

NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

The inhibition of TNF-α-induced NF-κB activation by marine natural products

The Role of Glycogen Synthase Kinase 3-β in Immunity and Cell Cycle: Implications in Esophageal Cancer

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