NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms

Yu, Li; Li, Ling; Medeiros, L. Jeffrey; Young, Ken H.

doi:10.1016/j.blre.2016.10.001

Cited by 88 publications

(67 citation statements)

References 170 publications

(197 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As expected, the phosphorylation levels of IκB α were also significantly increased in rumen epithelial cells treated with histamine. Subsequently, phosphorylation and proteasome-mediated degradation of IκB proteins would activate NF-κB and facilitate its transportation to nuclear [28]. This trend was observed, histamine significantly increased the protein and mRNA expression and transcriptional activity of NF-κB.…”

Section: Discussionmentioning

confidence: 68%

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

Sun

Xue

Chen

et al. 2017

Cell Physiol Biochem

103

View full text Add to dashboard Cite

Background/Aims: Subacute ruminal acidosis (SARA) is a common disease in highproducing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.X. Sun and X Yuan contributed equally to this study.

show abstract

Section: Discussionmentioning

confidence: 68%

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

Sun

Xue

Chen

et al. 2017

Cell Physiol Biochem

103

View full text Add to dashboard Cite

show abstract

“…As a critical transcription factor, constitutive NF-κB activity was observed in a larger number of human cancers and promoted growth and progression, including that in prostate cancer [25,26,46]. In addition, HOTAIR expression was associated with induced proliferation and aggressive behavior of cancer cells, resulting in poor prognosis [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

“…Given the tumor promoter roles of NF-κB [25,26] and LncRNA HOTAIR [20,21], we evaluated the effects of PPI with or without enzalutamide. We showed that PPI decreased NF-κB subunit p65 protein expression ( Fig.…”

Section: Ppi Decreased the Protein Expression Levels Of P65 And Lncrnmentioning

confidence: 99%

“…NF-κB is activated by various extracellular signals and regulates the expression of different genes [23,24]. Constitutive NF-κB activity was observed in a large number of human cancers and shown to play an important role in the process from inflammation to carcinogenesis; constitutive NF-κB activation is a targeted intervention in various malignancies, including prostate cancer [25,26]. Limited studies have reported the potential role of NF-κB in mediating the therapeutic effects of PPI [27].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

Xiang

Zou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, reportedly exhibits antitumor effects. However, the detailed mechanism underlying PPI, particularly in enhancing the effect of the androgen receptor inhibitor enzalutamide in controlling castration-resistant prostate cancer (CRPC) has not been explored. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) expression was measured by quantitative real time-PCR (qRT-PCR). Western blot analysis was performed to determine the protein expression levels of MUC1, p65, and p50. Silencing of HOTAIR was evaluated using the siRNA procedure. The promoter activity of the MUC1 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expression of HOTAIR, p65, and MUC1 was conducted by transient transfection assay. A xenograft tumor model in nude mice was used to further evaluate the effect of the combination of PPI and enzalutamide in vivo. Results: We showed that PPI significantly inhibited growth and induced cell cycle arrest in CRPC cells. PPI also decreased p65 and MUC1 protein expression and reduced HOTAIR expression. Exogenously expressed p65 resisted the PPI-inhibited expression of HOTAIR, whereas silenced HOTAIR reduced MUC1 protein but exerted no effect on the expression of p65 and p50 proteins. Conversely, exogenously expressed HOTAIR resisted the PPI-inhibited MUC1 protein expression, and excessive expression of MUC1 antagonized the PPI-inhibited cell growth. Notably, PPI combined with enzalutamide exerted a synergistic effect. Consistent with this finding, PPI inhibited tumor growth, HOTAIR expression, as well as p65 and MUC1 protein expressions in vivo. Conclusions: Our results indicate that PPI inhibits the growth of CRPC cells by inhibiting p65 protein and concomitantly reducing HOTAIR expression, thereby suppressing MUC1 gene expression. The novel regulatory interaction of p65 and HOTAIR converge in the inhibition of MUC1 expression and overall PPI response. The combination of PPI and enzalutamide exhibits synergy. This study reveals a novel mechanism underlying the synergistic inhibitory effect of PPI and enzalutamide on the growth of CRPC cells.

show abstract

“…The target genes of the noncanonical NF-κB pathway function in lymphoid organogenesis, adaptive immunity, anti-inflammatory properties, and B-cell maturation. 18–20 …”

Section: Oncogenic Signaling Pathways In Lymphomas and Their Thermentioning

confidence: 99%

Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies

2017

Self Cite

View full text Add to dashboard Cite

Lymphoma is characterized by heterogeneous biology, pathologic features, and clinical outcome. This has been proven by accumulating pathologic and molecular evidence attributed to underlying aberrant alterations at genetic, epigenetic, transcriptional, protein, microenvironmental levels, and dysregulated oncogenic signaling pathways. In the era of precision medicine, targeting oncogenic pathways to design drugs and to optimize treatment regimens for the lymphoma patients is feasible and clinically significant. As such, further understanding of the biology and the mechanisms behind lymphoma development and identification of oncogenic pathway activation and pathway-based biomarkers to better design precise therapies are challenging but hopeful. Furthermore, pathway-based targeted therapies in combination with traditional chemotherapy, single specific targeted antibody therapy, and immunotherapy might raise the hope for the patients with lymphoma, especially for relapsed and refractory lymphoma patients.

show abstract

NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms

Cited by 88 publications

References 170 publications

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies

Contact Info

Product

Resources

About