NF-κB Fans the Flames of Lung Carcinogenesis

ArticleinCancer Prevention Research 3(4):403-5 · March 2010with17 Reads
DOI: 10.1158/1940-6207.CAPR-10-0042 · Source: PubMed
This perspective on Deng et al. (beginning on p. 424 in this issue of the journal) examines the link between NF-kappa B and lung tumorigenesis. Experiments in genetically engineered mouse models of lung cancers are elucidating protumorigenic roles of NF-kappa B activation in lung cancer pathogenesis. Our growing understanding of the tumor-promoting NF-kappa B downstream effector pathways could lead to the development of novel approaches for lung cancer therapy and chemoprevention. Cancer Prev Res; 3(4); 403-5. (C)2010 AACR.
    • "A significant reduction in the levels of these cytokines and infiltration of immune cells was observed in lung cancer cells in response to blocking of NF-jB by proteasome inhibitor MG-132. Furthermore, reduction in tumor size was also observed in response to blocking of NF-jB (Chen et al. 2011; Takahashi et al. 2010; Wong et al. 2010 ) Factors associated with angiogenesis like VEGF, TNF-a, IL-8, IL-6, MCP-1, and matrix metalloproteinases are also activated by NF-jB in lung tumor cells (Chen et al. 2011; Grivennikov et al. 2010; Wang and Lin 2008) (Fig. 6d). Since NF-jB promotes angiogenesis and is involved in cancer progression, it acts as a major target for the therapeutic purposes. "
    [Show abstract] [Hide abstract] ABSTRACT: The nuclear factor (NF)-κB family of transcription factors are ubiquitous and pleiotropic molecules that regulate the expression of more than 150 genes involved in a broad range of processes including inflammation, immunity, cell proliferation, differentiation, and survival. The chronic activation or dysregulation of NF-κB signaling is the central cause of pathogenesis in many disease conditions and, therefore, NF-κB is a major focus of therapeutic intervention. Because of this, understanding the relationship between NF-κB and the induction of various downstream signaling molecules is imperative. In this review, we provide an updated synopsis of the role of NF-κB in DNA repair and in various ailments including cardiovascular diseases, HIV infection, asthma, herpes simplex virus infection, chronic obstructive pulmonary disease, and cancer. Furthermore, we also discuss the specific targets for selective inhibitors and future therapeutic strategies.
    Article · May 2016
    • "NF-κB regulated genes include cytokines, adhesion molecules, angiogenic factors, anti-apoptotic factors, and matrix metalloproteinases (MMPs), which are involved in different steps of carcinogenesis. It has been suggested that NF-κB promotes lung cancer mainly through mediating inflammatory cytokines secretion to establish a cancer-prone inflammatory microenvironment [48]. Similarly, NF-κB pathways play a crucial role in the pathogenesis/development of COPD by increasing the release of pro-inflammatory mediators leading to chronic inflammation in the lung. "
    [Show abstract] [Hide abstract] ABSTRACT: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.
    Full-text · Article · Feb 2013
    • "For instance, corilagin was recently found to inhibit NF-kappaB functions [24] . This is very important , since NF-kappaB is involved in several human pathologies, including osteoporosis [52], rheumatoid arthritis [53] and cancer [54,55]. In addition, NF-kappaB is one among the master transcription factors responsible for inflammation in cystic fibrosis cells infected with P. aeruginosa [10]. "
    [Show abstract] [Hide abstract] ABSTRACT: Corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), a gallotannin identified in several plants, including Phyllanthus urinaria, has been shown to exhibit versatile medicinal activities. As far as possible anti-inflammatory effects of corilagin, only few reports are available, and the potential use of corilagin as possible therapeutic molecule for cystic fibrosis has not been evaluated. In the present paper we report experiments aimed at determining the activity of corilagin on nuclear factor kappaB (NF-kappaB) binding to DNA target and on the expression of the major pro-inflammatory gene involved in cystic fibrosis, interleukin-8 (IL-8). Both IL-8 mRNA content and IL-8 protein secretion were analyzed in cystic fibrosis bronchial IB3-1 cells stimulated by tumor necrosis factor-alpha (TNF-alpha), one of the most potent pro-inflammatory agents. The data obtained demonstrate that corilagin binds to NF-kappaB, inhibits NF-kappaB/DNA interactions and affects IL-8 gene expression in TNF-alpha treated IB3-1 cells. In addition, corilagin inhibits TNF-alpha induced secretion of MCP-1 and RANTES, exhibiting low or no effect on the release of G-CSF, IL-6 and VEGF. Therefore, corilagin might be of interest for experimental anti-inflammatory therapy of cystic fibrosis.
    Full-text · Article · May 2012
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