Relationship between copper(ii) complexes with FomA adhesin fragments ofF. nucleatumand colorectal cancer. Coordination pattern and ability to promote ROS production

2018 ◽  
Vol 47 (15) ◽  
pp. 5445-5458 ◽  
Author(s):  
M. K. Lesiów ◽  
U. K. Komarnicka ◽  
K. Stokowa-Sołtys ◽  
K. Rolka ◽  
A. Łęgowska ◽  
...  

The copper(ii) binding of the fragments of FomA was studied. Complexes stimulate the CT26 cell line to produce ROS which lead to oxidative stress.

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Gitana Maria Aceto ◽  
Teresa Catalano ◽  
Maria Cristina Curia

The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into in situ carcinoma through the interactions between environmental and genetic factors. CRC incidence rates are constantly increased for young adult patients presenting an advanced tumor stage. The majority of CRCs arise from colonic adenomas originating from aberrant cell proliferation of colon epithelium. Endoscopic polypectomy represents a tool for early detection and removal of polyps, although the occurrence of cancers after negative colonoscopy shows a significant incidence. It has long been recognized that the aberrant regulation of Wingless/It (Wnt)/β-Catenin signaling in the pathogenesis of colorectal cancer is supported by its critical role in the differentiation of stem cells in intestinal crypts and in the maintenance of intestinal homeostasis. For this review, we will focus on the development of adenomatous polyps through the interplay between renewal signaling in the colon epithelium and reactive oxygen species (ROS) production. The current knowledge of molecular pathology allows us to deepen the relationships between oxidative stress and other risk factors as lifestyle, microbiota, and predisposition. We underline that the chronic inflammation and ROS production in the colon epithelium can impair the Wnt/β-catenin and/or base excision repair (BER) pathways and predispose to polyp development. In fact, the coexistence of oxidative DNA damage and errors in DNA polymerase can foster C>T transitions in various types of cancer and adenomas, leading to a hypermutated phenotype of tumor cells. Moreover, the function of Adenomatous Polyposis Coli (APC) protein in regulating DNA repair is very important as therapeutic implication making DNA damaging chemotherapeutic agents more effective in CRC cells that tend to accumulate mutations. Additional studies will determine whether approaches based on Wnt inhibition would provide long-term therapeutic value in CRC, but it is clear that APC disruption plays a central role in driving and maintaining tumorigenesis.


2020 ◽  
Author(s):  
Elena Chierto ◽  
Giulia Cristinziano ◽  
Francesca Sapone ◽  
Delphine Meffre ◽  
Mehrnaz Jafarian-Tehrani

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255120
Author(s):  
Giulia Vecchiotti ◽  
Sabrina Colafarina ◽  
Massimo Aloisi ◽  
Osvaldo Zarivi ◽  
Piero Di Carlo ◽  
...  

The potential risks of environmental nanoparticles (NPs), in particular Polystyrene Nanoparticles (PNPs), is an emerging problem; specifically, the interaction of PNPs with intestinal cells has not been characterized so far. The mechanism by which polystyrene particles are transferred to humans has not yet been clarified, whether directly through ingestion from contaminated food. We evaluated the interaction between PNPs and colorectal adenocarcinoma cells (HCT116). Cells were exposed to different concentrations of PNPs, metabolic activity and the consequent cytotoxic potential were assessed through viability test; we evaluated the PNP genotoxic potential through the Cytokinesis-Block Micronucleus cytome (CBMN cyt) assay. Finally, we detected Reactive Oxygen Species (ROS) production after NPs exposure and performed Western Blot analysis to analyze the enzymes (SOD1, SOD2, Catalase, Glutathione Peroxidase) involved in the cell detoxification process that comes into play during the cell-PNPs interaction. This work analyzes the cyto and genotoxicity of PNPs in the colorectal HCT116 cell line, in particular the potential damage from oxidative stress produced by PNPs inside the cells related to the consequent nuclear damage. Our results show moderate toxicity of PNPs both in terms of ROS production and DNA damage. Further studies will be needed on different cell lines to have a more complete picture of the impact of environmental pollution on human health in terms of PNPs cytotoxicity and genotoxicity.


2018 ◽  
Vol 16 (2) ◽  
pp. 106-112 ◽  
Author(s):  
Rossella Gratton ◽  
Paola Maura Tricarico ◽  
Rafael Lima Guimaraes ◽  
Fulvio Celsi ◽  
Sergio Crovella

Background:Lopinavir and Ritonavir (LPV/r) treatment is widely used to prevent HIV mother-to-child transmission. Nevertheless, studies related to the impact of these compounds on patients, in particular in the foetus and newborns, are strictly required due to the controversial findings reported in the literature concerning possible neurologic side effects following the administration of these drugs.Objectives:In our study, we evaluated the impact of LPV/r treatment on the human glioblastoma U- 87 MG cell line.Methods:In order to evaluate the influence of Lopinavir and Ritonavir in terms of oxidative stress (ROS production), mitochondrial morphology and apoptotic cell death, the latter either in the presence or in the absence of caspase-3 and -9 inhibitors, we treated U-87 MG with increasing doses (0.1-1-10-25-50 µM) of Lopinavir and Ritonavir for 24h, either in single formulation or in combination. ROS production was measured by flow cytometry using H2DCFDA dye, mitochondrial morphology was evaluated using MitoRed dye and apoptotic cell death was monitored by flow cytometry using Annexin V-FITC and Propidium Iodide.Results:We observed that co-treatment with Lopinavir and Ritonavir (25 and 50 µM) promoted a significant increase in ROS production, caused mitochondrial network damage and induced apoptosis in a caspase-independent manner.Conclusion:Based on our findings, concordant with others reported in the literature, we hypothesize that LPV/r treatment could not be entirely free from side effects, being aware of the need of validation in in vivo models, necessary to confirm our results.


Author(s):  
Hadis Alidadi ◽  
Maryam Shirani ◽  
Azin Samimi ◽  
Anayatollah Salimi ◽  
Atefeh Ashtari ◽  
...  

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