scholarly journals Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies

2020 ◽  
Vol 13 (8) ◽  
pp. 194 ◽  
Author(s):  
Malgorzata Sztiller-Sikorska ◽  
Malgorzata Czyz
Keyword(s):  
Cancer Cells ◽  
Nuclear Factor Kappa B ◽  
Acquired Resistance ◽  
Complementary Therapy ◽  
Mechanisms Of Action ◽  
Nuclear Factor ◽  
Development Of Resistance ◽  
Current State ◽  
Anti Cancer ◽  
Survival Signaling

Primary and acquired resistance of cancer to therapy is often associated with activation of nuclear factor kappa B (NF-κB). Parthenolide (PN) has been shown to inhibit NF-κB signaling and other pro-survival signaling pathways, induce apoptosis and reduce a subpopulation of cancer stem-like cells in several cancers. Multimodal therapies that include PN or its derivatives seem to be promising approaches enhancing sensitivity of cancer cells to therapy and diminishing development of resistance. A number of studies have demonstrated that several drugs with various targets and mechanisms of action can cooperate with PN to eliminate cancer cells or inhibit their proliferation. This review summarizes the current state of knowledge on PN activity and its potential utility as complementary therapy against different cancers.

scholarly journals The Potential of Lactobacillus spp. for Modulating Oxidative Stress in the Gastrointestinal Tract

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 610 ◽  
Author(s):  
Yanzhuo Kong ◽  
Kenneth J. Olejar ◽  
Stephen L. W. On ◽  
Venkata Chelikani
Keyword(s):  
Oxidative Stress ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mechanisms Of Action ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Pathogenic Microorganisms ◽  
Gi Tract ◽  
Lactobacillus Spp

The gastrointestinal (GI) tract is crucial for food digestion and nutrient absorption in humans. However, the GI tract is usually challenged with oxidative stress that can be induced by various factors, such as exogenous pathogenic microorganisms and dietary alterations. As a part of gut microbiota, Lactobacillus spp. play an important role in modulating oxidative stress in cells and tissues, especially in the GI tract. Oxidative stress is linked with excessive reactive oxygen species (ROS) that can be formed by a few enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). The redox mechanisms of Lactobacillus spp. may contribute to the downregulation of these ROS-forming enzymes. In addition, nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf-2) and nuclear factor kappa B (NF-κB) are two common transcription factors, through which Lactobacillus spp. modulate oxidative stress as well. As oxidative stress is closely associated with inflammation and certain diseases, Lactobacillus spp. could potentially be applied for early treatment and amelioration of these diseases, either individually or together with prebiotics. However, further research is required for revealing their mechanisms of action as well as their extensive application in the future.

scholarly journals Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010 ◽  
Vol 23 (3) ◽  
pp. 590-615 ◽  
Author(s):  
Soichiro Kanoh ◽  
Bruce K. Rubin
Keyword(s):  
Nuclear Factor Kappa B ◽  
Biological Activities ◽  
Mechanisms Of Action ◽  
Nuclear Factor ◽  
Diffuse Panbronchiolitis ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Regulation Of Cell Cycle ◽  
Immunomodulatory Therapies

SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

scholarly journals A Positive Feedback Loop Between Gastric Cancer Cells and Tumor-associated Macrophage Induces Malignancy Progression

2022 ◽  
Author(s):  
Haiyan Piao ◽  
Lingfeng Fu ◽  
Yang Liu ◽  
Yue Wang ◽  
Xiangyu Meng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Factor Kappa B ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Positive Feedback Loop ◽  
Nuclear Factor Kappa

Abstract Background: Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood.Methods: Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of CXCL8 in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites.The corresponding functions were verified in the complementation test and in vivo animal experiment.Results: Our results revealed that Hypoxia triggered macrophage secreted C-X-C Motif Chemokine Ligand 8 (CXCL8), which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 (CXCR1/2) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 (IL-10). Correspondingly, IL-10 induced the M2-type polarization of macrophages through the Nuclear Factor kappa B (NF-κB) pathway-dependent mechanism and continued to increase the expression and secretion of CXCL8 through the transcription factor Nuclear Factor Kappa B Subunit 1 (NFKB1, p50). It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient's pessimistic outcome.Conclusion: Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.

scholarly journals Cyclooxygenase 2 Promotes Proliferation and Invasion in Ovarian Cancer Cells via the PGE2/NF-κB Pathway

2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 1S-13S ◽  
Author(s):  
Xiao Zhang ◽  
Keqin Yan ◽  
Lin Deng ◽  
Jing Liang ◽  
Haiyan Liang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prostaglandin E2 ◽  
Cancer Cells ◽  
Nuclear Factor Kappa B ◽  
Cyclooxygenase 2 ◽  
High Expression ◽  
Ovarian Cancer Cells ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Proliferation And Invasion

Ovarian cancer is the leading cause of death among gynecological malignancies. Cyclooxygenase 2 is widely expressed in various cancer cells and participates in the occurrence and development of tumors by regulating a variety of downstream signaling pathways. However, the function and molecular mechanisms of cyclooxygenase 2 remain unclear in ovarian cancer. Here, we demonstrated that cyclooxygenase 2 was highly expressed in ovarian cancer and the expression level was highly correlated with ovarian tumor grades. Further, ovarian cancer cells with high expression of cyclooxygenase 2 exhibit enhanced proliferation and invasion abilities. Specifically, cyclooxygenase 2 promoted the release of prostaglandin E2 upregulated the phosphorylation levels of phospho-nuclear factor-kappa B p65. Celecoxib, AH6809, and BAY11-7082 all can inhibit the promoting effect of cyclooxygenase 2 on SKOV3 and OVCAR3 cell proliferation and invasion. Besides, celecoxib inhibited SKOV3 cell growth in the xenograft tumor model. These data suggest that high expression of cyclooxygenase 2 promotes the proliferation and invasion of ovarian cancer cells through the prostaglandin E2/nuclear factor-kappa B signaling pathway. Cyclooxygenase 2 may be a potential therapeutic target for the treatment of ovarian cancer.

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