scholarly journals Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53

2021 ◽  
Vol 11 (6) ◽  
pp. 509
Author(s):  
Sandra Ríos-Arrabal ◽  
Jose D. Puentes-Pardo ◽  
Sara Moreno-SanJuan ◽  
Ágata Szuba ◽  
Jorge Casado ◽  
...  

Heme oxygenase-1 (HO-1) is an antioxidant protein implicated in tumor progression, metastasis, and resistance to therapy. Elevated HO-1 expression is associated with stemness in several types of cancer, although this aspect has not yet been studied in colorectal cancer (CRC). Using an in vitro model, we demonstrated that HO-1 overexpression regulates stemness and resistance to 5-FU treatment, regardless of p53. In samples from CRC patients, HO-1 and endothelin converting enzyme-1 (ECE-1) expression correlated significantly, and p53 had no influence on this result. Carbon monoxide (CO) activated the ECE-1/endothelin-1 (ET-1) pathway, which could account for the protumoral effects of HO-1 in p53 wild-type cells, as demonstrated after treatment with bosentan (an antagonist of both ETRA and ETRB endothelin-1 receptors). Surprisingly, in cells with a non-active p53 or a mutated p53 with gain-of-function, ECE-1-produced ET-1 acted as a protective molecule, since treatment with bosentan led to increased efficiency for spheres formation and percentage of cancer stem cells (CSCs) markers. In these cells, HO-1 could activate or inactivate certain unknown routes that could induce these contrary responses after treatment with bosentan in our cell model. However more research is warranted to confirm these results. Patients carrying tumors with a high expression of both HO-1 and ECE-1 and a non-wild-type p53 should be considered for HO-1 based-therapies instead of ET-1 antagonists-based ones.

2018 ◽  
Vol 17 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Arjun Jain ◽  
Shali Chen ◽  
Hannah Yong ◽  
Subrata Chakrabarti

Nanomedicine ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. 331-344 ◽  
Author(s):  
Víctor López-Dávila ◽  
Tarig Magdeldin ◽  
Hazel Welch ◽  
Miriam Victoria Dwek ◽  
Ijeoma Uchegbu ◽  
...  

2014 ◽  
Vol 5 ◽  
pp. 204173141454418 ◽  
Author(s):  
Tarig Magdeldin ◽  
Víctor López-Dávila ◽  
Cecile Villemant ◽  
Grant Cameron ◽  
Rosemary Drake ◽  
...  

2010 ◽  
Vol 17 (5) ◽  
pp. 370-378 ◽  
Author(s):  
Hidetaka Hara ◽  
Nathalie Campanile ◽  
Hao-Chih Tai ◽  
Cassandra Long ◽  
Burcin Ekser ◽  
...  

2020 ◽  
Vol 8 (9) ◽  
pp. 1374
Author(s):  
María A. Núñez-Sánchez ◽  
Joan Colom ◽  
Lauren Walsh ◽  
Colin Buttimer ◽  
Andrei Sorin Bolocan ◽  
...  

An intestinal epithelium model able to produce mucus was developed to provide an environment suitable for testing the therapeutic activity of gut bacteriophages. We show that Enterococcus faecalis adheres more effectively in the presence of mucus, can invade the intestinal epithelia and is able to translocate after damaging tight junctions. Furthermore, Enterococcus phage vB_EfaM_A2 (a member of Herelleviridae that possesses virion associated immunoglobin domains) was found to translocate through the epithelium in the presence and absence of its host bacteria. Phage A2 protected eukaryotic cells by reducing mortality and maintaining the structure of the cell layer structure. We suggest the mammalian cell model utilized within this study as an adaptable in vitro model that can be employed to enable a better understanding of phage–bacteria interactions and the protective impact of phage therapy relating to the intestinal epithelium.


2007 ◽  
Vol 143 (1) ◽  
pp. 94-98 ◽  
Author(s):  
Peter S. Yoo ◽  
Abby L. Mulkeen ◽  
Alan Dardik ◽  
Charles H. Cha

2008 ◽  
Vol 28 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Jocelyne Franchi ◽  
Clarisse Marteau ◽  
Claire Crola Da Silva ◽  
Michèle Mitterrand ◽  
Patrice André ◽  
...  

Chemical and physical stimuli trigger a cutaneous response by first inducing the main epidermal cells, keratinocytes, to produce specific mediators that are responsible for the initiation of skin inflammation. Activation modulates cell communication, namely leucocyte recruitment and blood-to-skin extravasation through the selective barrier of the vascular ECs (endothelial cells). In the present study, we describe an in vitro model which takes into account the various steps of human skin inflammation, from keratinocyte activation to the adhesion of leucocytes to dermal capillary ECs. Human adult keratinocytes were subjected to stress by exposure to UV irradiation or neuropeptides, then the conditioned culture medium was used to mimic the natural micro-environmental conditions for dermal ECs. A relevant in vitro model must include appropriate cells from the skin. This is shown in the present study by the selective reaction of dermal ECs compared with EC lines from distinct origins, in terms of leucocyte recruitment, sensitivity to stress and nature of the stress-induced secreted mediators. This simplified model is suitable for the screening of anti-inflammatory molecules whose activity requires the presence of various skin cells.


Author(s):  
Clara Bonafini ◽  
Marta Marzotto ◽  
Debora Olioso ◽  
Paolo Bellavite

Background: A proinflammatory environment is a hallmark of several neurodegenerative diseases where astrocyte involvement is also well established. Astrocytes and microglia in central nervous system are mainly involved in the release of cytokines, oxygen free radicals and nitric oxide (NO). Several studies on C6 astroglioma cells, a widely used in vitro model for these events, demonstrated that co-stimulation of this cell line with bacterial lipopolysaccharide (LPS) and interferon gamma (IFN-) induces a synergistic nitric oxide synthase (iNOS) expression.1 In our laboratory we are using this versatile cell model in order to carefully investigate dose-response effects of various putative agonists or inhibitors and to assess the possible changes provoked in those agents by different procedures of dilution and succussion (agitation) (potentization according to the homeopathic terminology).


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