Role of the NF&amp;kappa;B-signaling pathway in cancer

Xia, Longzheng; Tan, Shiming; Zhou, Yujuan; Lin, Jingguan; Wang, Heran; Oyang, Linda; Tian, Yutong; Liu, Lu; Su, Min; Wang, Hui; Cao, Deliang; Lu, Qianjin

doi:10.2147/ott.s161109

Cited by 366 publications

(248 citation statements)

References 147 publications

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“…The nuclear factor kappa B (NFκB) family comprises of five DNA-binding proteins (p50, p52, p65, cRel, and RelB) that differentially modulate the transcription of genes that are involved in various cellular processes such as inflammation, migration, invasion, angiogenesis, proliferation, and apoptosis [172,173]. The continuous activation of NFκB has been reported in different types of cancers.…”

Section: Nuclear Factor Kappa B (Nf-κb)mentioning

confidence: 99%

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

131

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Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial-mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5 AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.

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Section: Nuclear Factor Kappa B (Nf-κb)mentioning

confidence: 99%

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

131

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“…It is well accepted now that low-grade chronic inflammation is a major cause for a number of diseases, including cancer [5,6]. The transcription factor nuclear factor-kappaB (NF-κB), as a common responder to varied stress stimuli, leading to chronic low grade inflammation, plays a key role here [7,8]. This master regulator of inflammation is located as an inactive form in the cytoplasm and, after activation, shuttles to the nucleus.…”

Section: Introductionmentioning

confidence: 99%

“…NF-κB is activated by various cytokines, pathogens or growth factors [8,11]. Previous studies have shown that TNF-β (lymphotoxin), a member of the tumor necrosis factor family, induces inflammatory effects in CRC cells with a similar potency to TNF-α [12,13].…”

Section: Introductionmentioning

confidence: 99%

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

et al. 2019

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Objective: Natural polyphenol Calebin A has been recently discovered as a novel derivate from turmeric with anti-cancer potential. Pro-inflammatory cytokine TNF-β (lymphotoxin α) is a stimulant for cancer cell malignity via activation of NF-κB pathway, also in colorectal cancer (CRC). Here, we investigated the potential of Calebin A to suppress TNF-β-induced NF-κB signalling in CRC. Materials and Methods: Three distinct CRC cell lines (HCT116, RKO, SW480) were treated in monolayer or 3-dimensional alginate culture with TNF-β, Calebin A, curcumin, BMS-345541, dithiothreitol (DTT) or antisense oligonucleotides-(ASO) against NF-κB. Results: Calebin A suppressed dose-dependent TNF-β-induced CRC cell vitality and proliferation in monolayer culture. Further, in alginate culture, Calebin A significantly suppressed TNF-β-enhanced colonosphere development, as well as invasion and colony formation of all three CRC cell lines investigated. Calebin A specifically blocked TNF-β-induced activation and nuclear translocation of p65-NF-κB, similar to curcumin (natural NF-κB inhibitor), BMS-345541 (specific IKK inhibitor) and ASO-NF-κB. Moreover, Immunofluorescence and Immunoblotting showed that Calebin A, similar to curcumin or BMS-345541 suppressed TNF-β-induced activation and nuclear translocation of p65-NF-κB and the transcription of NF-κB-promoted biomarkers associated with proliferation, migration and apoptosis, in a doseand time-dependent manner. Those findings were potentiated by the specific treatment of extracted nuclei with DTT, which abrogated Calebin A-mediated nuclear p65-NF-κB-inhibition and restored p65-NF-κB-activity in the nucleus. Conclusion: Overall, these results demonstrate, for the first time, that multitargeted Calebin A has an anti-cancer capability on TNF-β-induced malignities through inhibitory targeting of NF-κB activation in the cytoplasm, as well as by suppressing the binding of p65-NF-κB to DNA.

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“…The effects of NFκB-signaling on patient outcome are yet to be determined, but some studies indicate that chronic activation promotes a tumor growth-favorable environment. For example, studies have shown that NFκB activity can promote tumor cell, can suppress apoptosis, and can enhance vascular growth [12,13]. Furthermore, it can energize the immune system in certain circumstances [13].…”

Section: Introductionmentioning

confidence: 99%

“…For example, studies have shown that NFκB activity can promote tumor cell, can suppress apoptosis, and can enhance vascular growth [12,13]. Furthermore, it can energize the immune system in certain circumstances [13]. However, contradicting results for its role in cancer has also been documented; one recurring theme in immunology is that chronic proinflammatory signaling can contribute to carcinogenesis, while acute signaling can cause antitumor immune responses [14].…”

Section: Introductionmentioning

confidence: 99%

TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling

Heiniö

Havunen²,

Santos

et al. 2020

Cells

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In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment.

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Role of the NFκB-signaling pathway in cancer

Cited by 366 publications

References 147 publications

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling

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