scholarly journals Terminalia catappaExerts Antimetastatic Effects on Hepatocellular Carcinoma through Transcriptional Inhibition of Matrix Metalloproteinase-9 by Modulating NF-κB and AP-1 Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Chao-Bin Yeh ◽  
Ming-Ju Hsieh ◽  
Yih-Shou Hsieh ◽  
Ming-Hsien Chien ◽  
Pen-Yuan Lin ◽  
...  

High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified thatTerminalia catappaleaf extracts (TCE) exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9). Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1.

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249544
Author(s):  
Rana Al-Sadi ◽  
Jessica Engers ◽  
Mohammad Haque ◽  
Steven King ◽  
Deemah Al-Omari ◽  
...  

Background Matrix Metalloproteinase-9 (MMP-9) has been shown to play a key role in mediating inflammation and tissue damage in inflammatory bowel disease (IBD). In patients with IBD, the intestinal tight junction (TJ) barrier is compromised as characterized by an increase in intestinal permeability. MMP-9 is elevated in intestinal tissue, serum and stool of patients with IBD. Previous studies from our laboratory showed that MMP-9 causes an increase in intestinal epithelial TJ permeability and that the MMP-9 induced increase in intestinal permeability is an important pathogenic factor contributing to the development of intestinal inflammation in IBD. However, the intracellular mechanisms that mediate the MMP-9 modulation of intestinal barrier function remain unclear. Aims The main aim of this study was to further elucidate the molecular mechanisms involved in MMP-9 induced increase in intestinal epithelial TJ permeability using Caco-2 monolayers as an in-vitro model system. Results MMP-9 induced increase in Caco-2 TJ permeability was associated with activation and cytoplasmic-to-nuclear translocation of NF-κB p65. Knocking-down NF-κB p65 by siRNA transfection prevented the MMP-9 induced expression of the NF-κB target gene IL-8, myosin light chain kinase (MLCK) protein expression, and subsequently prevented the increase in Caco-2 TJ permeability. In addition, the effect of MMP-9 on Caco-2 intestinal epithelial TJ barrier function was not mediated by apoptosis or necrosis. Conclusion Our data show that the MMP-9 induced disruption of Caco-2 intestinal epithelial TJ barrier function is regulated by NF-κB pathway activation of MLCK.


Vascular ◽  
2021 ◽  
pp. 170853812098629
Author(s):  
Bálint Nagy ◽  
Elettra Engblom ◽  
Marijana Matas ◽  
Péter Maróti ◽  
Tamás Kőszegi ◽  
...  

Objectives Perioperative stress affects the outcome of carotid endarterectomy performed under regional anesthesia. Here we aimed to explore the temporal profile of the stress marker cortisol and its relationship to high-sensitivity troponin-T, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and S100B as an indicator of blood–brain barrier alteration in the systemic circulation. Methods Prospective part of the study: a total of 31 patients with significant carotid stenosis scheduled for carotid endarterectomy in regional anesthesia were enrolled. Follow-up part of the study and retrospective analysis of the outcome: each patient was followed up to five years and morbidity as well as mortality data were collected from an electronic database. Blood samples from each patient were serially taken; prior to surgery (T1), at the time of reperfusion (T2), 24 h (T3) and 72 h later postoperatively (T4), then the plasma concentration of each biomarker was measured. Besides, the clinical and surgical factors and perioperative adverse events were recorded. Results More positive correlations were found between: the early change of S100B (T2–T1) and late change in plasma cortisol level (T4–T3) (r = 0.403; p < 0.05); the early change of cortisol (T2–T1) and the early postoperative change of plasma matrix metalloproteinase-9 level (T3–T2) (r = 0.432; p = 0.01); the plasma concentration of tissue inhibitor of metalloproteinase-1 at 24 postoperative hours and the late change in plasma high-sensitivity troponin-T level (T4–T3) (r = 0.705; p < 0.001). Five patients needed an intraoperative shunt in whom the high-sensitivity troponin-T was elevated even prior to surgery, but definitive stroke never occurred. Plasma matrix metalloproteinase-9 concentration at reperfusion independently predicted the five-year mortality with a cut-off value of 456 ng/ml (sensitivity: 86%, specificity: 84%, area 0.887, p = 0.002). Conclusions A higher intraoperative change in S100B level reflecting carotid endarterectomy induced acute silent brain ischemia was associated with more pronounced post-operative change of cortisol. An early elevation of cortisol was found to be associated with a delayed increase of matrix metalloproteinase-9. Importantly, an increased high-sensitivity troponin-T even prior to carotid endarterectomy may predict clamp intolerance, and elevated matrix metalloproteinase-9 at reperfusion suggests a poor outcome.


2010 ◽  
Vol 16 (5) ◽  
pp. 621-630 ◽  
Author(s):  
Deniz Nart ◽  
Banu Yaman ◽  
Funda Yılmaz ◽  
Murat Zeytunlu ◽  
Zeki Karasu ◽  
...  

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