Multiparametric temporal analysis of the Caco-2/TC7 demonstrated functional and differentiated monolayers as early as 14 days of culture

Zeller, Perrine; Bricks, Thibault; Jacques, Sébastien; Anton, Pauline M.; Leclerc, Éric

doi:10.1016/j.ejps.2015.02.013

Cited by 14 publications

(10 citation statements)

References 40 publications

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“…Other experimental conditions, such as cellular differentiation and incubation time, must be taken into account because the cytokine expression varies depending on these parameters. As an example, the general inflammatory response is higher in proliferating cells compared with fully differentiated cells 60 , 61 .…”

Section: Discussionmentioning

confidence: 99%

Food Chemicals Disrupt Human Gut Microbiota Activity And Impact Intestinal Homeostasis As Revealed By In Vitro Systems

Defois

Ratel²,

Garrait

et al. 2018

Sci Rep

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Growing evidence indicates that the human gut microbiota interacts with xenobiotics, including persistent organic pollutants and foodborne chemicals. The toxicological relevance of the gut microbiota-pollutant interplay is of great concern since chemicals may disrupt gut microbiota functions, with a potential impairment of host homeostasis. Herein we report within batch fermentation systems the impact of food contaminants (polycyclic aromatic hydrocarbons, polychlorobiphenyls, brominated flame retardants, dioxins, pesticides and heterocyclic amines) on the human gut microbiota by metatranscriptome and volatolome i.e. “volatile organic compounds” analyses. Inflammatory host cell response caused by microbial metabolites following the pollutants-gut microbiota interaction, was evaluated on intestinal epithelial TC7 cells. Changes in the volatolome pattern analyzed via solid-phase microextraction coupled to gas chromatography-mass spectrometry mainly resulted in an imbalance in sulfur, phenolic and ester compounds. An increase in microbial gene expression related to lipid metabolism processes as well as the plasma membrane, periplasmic space, protein kinase activity and receptor activity was observed following dioxin, brominated flame retardant and heterocyclic amine exposure. Conversely, all food contaminants tested induced a decreased in microbial transcript levels related to ribosome, translation and nucleic acid binding. Finally, we demonstrated that gut microbiota metabolites resulting from pollutant disturbances may promote the establishment of a pro-inflammatory state in the gut, as stated with the release of cytokine IL-8 by intestinal epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Food Chemicals Disrupt Human Gut Microbiota Activity And Impact Intestinal Homeostasis As Revealed By In Vitro Systems

Defois

Ratel²,

Garrait

et al. 2018

Sci Rep

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“…We have established its ability to induce necroptosis by increasing ROS levels, which triggers cell death. Due to the spontaneous differentiation of Caco-2 cells to normal enterocytes after 15 days growing[32], we were able to compare its effect on both CRC and healthy tissue. Additionally, data obtained in 2D cell model were expanded by testing the antiproliferative effect of the compound on 3D spheroid model.…”

mentioning

confidence: 99%

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells

Mármol

Virumbrales-Muñoz

Medina-Quero

et al. 2017

Journal of Inorganic Biochemistry

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Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NCH)(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NCH)(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NCH)(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance.

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“…Incubation time was found to be crucial for the antiproliferative effect of the drug combination, since it induced significant changes in cell viability (p < 0.05) at short-time incubation (24 h) whereas for the gold complex these changes were not observed until 48 h. Moreover, the drug combination induced a 50% reduction on cell viability upon 48 h of incubation, whereas single agents reached that effect after 72 h. Caco-2 cells undergo spontaneous differentiation after reaching confluence and acquire the morphology and enzymatic profile of a mature enterocyte [22]. Thus, differentiated Caco-2 cells are considered as an acceptable model of the intestinal barrier and have been traditionally used to evaluate the toxicity of novel drugs on a non-cancerous model [23]. The drug combination and AP did not induce significant changes on cell proliferation of differentiated Caco-2 cells after long-term incubation (72 h) ( Figure S2), which might suggest that such combination displays selectivity for this cancer type.…”

Section: Acidic Polyphenols From R Canina Enhance the Antiproliferatmentioning

confidence: 99%

“…Caco-2 cells undergo spontaneous differentiation after reaching confluence and acquire the morphology and enzymatic profile of a mature enterocyte [22]. Thus, differentiated Caco-2 cells are considered as an acceptable model of the intestinal barrier and have been traditionally used to evaluate the toxicity of novel drugs on a non-cancerous model [23]. The drug combination and AP did not induce significant changes on cell proliferation of differentiated Caco-2 cells after long-term incubation (72 h) ( Figure S2), which might suggest that such combination displays selectivity for this cancer type.…”

Section: Drug Combination Triggers Apoptosis On Caco-2 Cellsmentioning

confidence: 99%

A Combination of Rosa Canina Extracts and Gold Complex Favors Apoptosis of Caco-2 Cells by Increasing Oxidative Stress and Mitochondrial Dysfunction

et al. 2019

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Given the alarming increase in colorectal cancer (CRC) worldwide, novel therapies are urgently needed. Plant-derived extracts have gained considerable interest in the last years due to their strong anticancer effect mediated by their unique bioactive compounds. Specifically, rosehips from Rosa canina have been successfully tested against several cancer models, including colon cancer. Moreover, gold derivatives are a promising alternative to the current platinum-based drugs commonly used in CRC chemotherapy due to their lack of affinity for DNA. Herein we have investigated the antitumor potential of a drug combination made of acidic polyphenols extracted from R. canina and the gold complex (Au(C≡C-2-NC5H4) (PTA)) in Caco-2 cell line as a model of CRC. The combination triggered strong apoptosis mediated by a blockage of the autophagic flux, which might be a consequence of a reactive oxygen species (ROS) increase and mitochondrial dysfunctionality. Our results suggest that the clinical application of plant polyphenols might enhance the anticancer effect of metallodrugs and reduce drug exposure time and therefore its side effects.

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Multiparametric temporal analysis of the Caco-2/TC7 demonstrated functional and differentiated monolayers as early as 14 days of culture

Cited by 14 publications

References 40 publications

Food Chemicals Disrupt Human Gut Microbiota Activity And Impact Intestinal Homeostasis As Revealed By In Vitro Systems

Food Chemicals Disrupt Human Gut Microbiota Activity And Impact Intestinal Homeostasis As Revealed By In Vitro Systems

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells

A Combination of Rosa Canina Extracts and Gold Complex Favors Apoptosis of Caco-2 Cells by Increasing Oxidative Stress and Mitochondrial Dysfunction

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