Soluble Epoxide Hydrolase as an Important Player in Intestinal Cell Differentiation

2020 ◽  
Vol 209 (4-6) ◽  
pp. 177-188
Author(s):  
Katerina Cizkova ◽  
Katerina Koubova ◽  
Tereza Foltynkova ◽  
Jana Jiravova ◽  
Zdenek Tauber
Keyword(s):  
Cell Differentiation ◽  
Colorectal Carcinoma ◽  
Cell Lines ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Intestinal Cell ◽  
Caco2 Cells ◽  
Important Player ◽  
Ht 29

There is growing evidence that soluble epoxide hydrolase (sEH) may play a role in cell differentiation. sEH metabolizes biologically highly active and generally cytoprotective epoxyeicosatrienoic acids (EETs), generated from arachidonic acid metabolism by CYP epoxygenases (CYP2C and CYP2J subfamilies), to less active corresponding diols. We investigated the effect of sEH inhibitor (TPPU) on the expression of villin, CYP2C8, CYP2C9, CYP2J2, and sEH in undifferentiated and in vitro differentiated HT-29 and Caco2 cell lines. The administration of 10 μM TPPU on differentiated HT-29 and Caco2 cells resulted in a significant decrease in expression of villin, a marker for intestinal cell differentiation. It was accompanied by a disruption of the brush border when microvilli appeared sparse and short in atomic force microscope scans of HT-29 cells. Although inhibition of sEH in differentiated HT-29 and Caco2 cells led to an increase in sEH expression in both cell lines, this treatment had an opposite effect on CYP2J2 expression in HT-29 and Caco2 cells. In addition, tissue samples of colorectal carcinoma and adjacent normal tissues from 45 patients were immunostained for sEH and villin. We detected a significant decrease in the expression of both proteins in colorectal carcinoma in comparison to adjacent normal tissue, and the decrease in both sEH and villin expression revealed a moderate positive association. Taken together, our results showed that sEH is an important player in intestinal cell differentiation.

HT-29 and Caco2 Cell Lines Are Suitable Models for Studying the Role of Arachidonic Acid-Metabolizing Enzymes in Intestinal Cell Differentiation

2019 ◽  
Vol 208 (1-2) ◽  
pp. 37-47
Author(s):  
Katerina Cizkova ◽  
Petr Birke ◽  
Jakub Malohlava ◽  
Zdenek Tauber ◽  
Zlata Huskova ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cell Differentiation ◽  
Cell Lines ◽  
Culture Conditions ◽  
Intestinal Cell ◽  
Caco2 Cell ◽  
Caco2 Cells ◽  
Ht 29

Introduction: Cytochrome (CYP) epoxygenases (CYP2C and CYP2J) and soluble epoxide hydrolase (sEH) participate in the metabolism of arachidonic acid and may also have a potential role in enterocyte differentiation. The first critical step in the study of intestinal cell differentiation is the determination of a suitable in vitro model, which must be as similar as possible to the conditions of a living organism. It is known that HT-29 and Caco2 cell lines derived from human colorectal carcinomas can differentiate into enterocyte-like cells in appropriate culture conditions. Material and Methods: We tested 4 different approaches of enterocyte-like differentiation and determined the most appropriate culture conditions for each model. Subsequently, the changes in the expression of CYP epoxygenases and sEH in undifferentiated and differentiated cells were measured by In-Cell ELISA. These results were compared with immunohistochemical profiles of expression of CYP epoxygenases and sEH in samples of human embryonic and fetal intestines as well as adult duodenum and colon. Results: Our results show that sodium butyrate (NaBt)-differentiated HT-29 cells and spontaneously differentiated Caco2 cells resemble CYP epoxygenases and sEH profiles, corresponding with different types of intestines. Conclusion: Our study revealed that the most suitable models for the study of the role of CYP epoxygenases and sEH expression in differentiation of intestinal epithelium are NaBt-differentiated HT-29 cells and spontaneously differentiated Caco2 cells.

Vitamin D as Radiosensitizer: A Review in Cell Line -

2020 ◽  
Vol 10 (6) ◽  
pp. 315-324
Author(s):  
Fahmi Radityamurti ◽  
Fauzan Herdian ◽  
Tiara Bunga Mayang Permata ◽  
Handoko Handoko ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Differentiation ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agent ◽  
Medical Literature ◽  
In Vitro Studies ◽  
Anti Cancer

Introduction: Vitamin D has been shown to have anti-cancer properties such as antioxidants, anti-proliferative, and cell differentiation. The property of vitamin D as an anticancer agent triggers researchers to find out whether vitamin D is useful as a radiosensitizer. Multiple studies have been carried out on cell lines in various types of cancer, but the benefits of vitamin D as a radiosensitizer still controversial. This paperwork aims to investigate the utilization of Vitamin D3 (Calcitriol) as radiosensitizer in various cell line through literature review.Methods: A systematic search of available medical literature databases was performed on in-vitro studies with Vitamin D as a radiosensitizer in all types of cell lines. A total of 11 in-vitro studies were evaluated.Results: Nine studies in this review showed a significant effect of Vitamin D as a radiosensitizer agent by promoting cytotoxic autophagy, increasing apoptosis, inhibiting of cell survival and proliferation, promoting gene in ReIB inhibition, inducing senescene and necrosis. The two remaining studies showed no significant effect in the radiosensitizing mechanism of Vitamin D due to lack of evidence in-vitro settings.Conclusion: Vitamin D have anticancer property and can be used as a radiosensitizer by imploring various mechanism pathways in various cell lines. Further research especially in-vivo settings need to be evaluated.

scholarly journals IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

2012 ◽  
Vol 2 (4) ◽  
Author(s):  
Kuppusamy Asokkumar ◽  
Lokeswari Prathyusha Tangella ◽  
Muthusamy Umamaheshwari ◽  
Thirumalaisamy Shivashanmugam ◽  
Varadharajan Subhadradevi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Chalcone Derivatives

In vitro and in silico investigation of anthocyanin derivatives as soluble epoxide hydrolase inhibitors

2018 ◽  
Vol 112 ◽  
pp. 961-967 ◽  
Author(s):  
Jang Hoon Kim ◽  
In Sook Cho ◽  
Jaihyuk Ryu ◽  
Ji Sun Lee ◽  
Jong Seong Kang ◽  
...  
Keyword(s):  
In Silico ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase Inhibitors

„IN VITRO“ AND „IN VIVO“ ANTITUMOR ACTIVITY OF PLATINUM(II) COMPLEXES WITH MALONIC ACID ON BREAST AND COLORECTAL CARCINOMA CELL LINES

2021 ◽  
Author(s):  
Andjela Franich ◽  
◽  
Milica Dimitrijević Stojanović ◽  
Snežana Rajković ◽  
Marina Jovanović ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Colorectal Carcinoma ◽  
Cell Lines ◽  
Tumor Model ◽  
Carcinoma Cells ◽  
Spectroscopic Techniques ◽  
Murine Cell Line ◽  
In Vivo Antitumor Activity

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is anion of malonic (mal, Pt1), 2-methylmalonic (Me-mal, Pt2), 2,2-dimethylmalonic (Me2-mal, Pt3) or 1,1- cyclobutanedicarboxylic (CBDCA, Pt4) acid while 5,6-epoxy-1,10-phen is bidentately coordinated 5,6-epoxy-5,6-dihydro-1,10-phenanthroline were synthesized and characterized by elemental microanalysis, IR, UV-Vis and NMR (1H and 13C) spectroscopic techniques. In vitro anticancer activity of novel platinum(II) complexes have been investigated on human and murine cancer cell lines, as well as normal murine cell line by MTT assay. The obtained results indicate that studied platinum(II) complexes exhibited strong cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. Complex Pt3 display stronger selectivity toward carcinoma cells in comparison to other tested platinum(II) complexes exhibiting beneficial antitumor activity mainly via the induction of apoptosis, as well as inhibition of cell proliferation and migration. Further study showed that Pt3 complex also carry significant in vivo antitumor activity in orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All results imply that these novel platinum(II) complexes have a good anti-tumor effect on breast and colorectal cancer in vivo and in vitro and the affinity to become possible candidates for treatment in anticancer therapy.

Soluble Epoxide Hydrolase Deletion Attenuated Nicotine-induced Arterial Stiffness via Limiting the Loss of SIRT1

2021 ◽  
Author(s):  
Shuiqing Hu ◽  
Jinlan Luo ◽  
Menglu Fu ◽  
Liman Luo ◽  
Yueting Cai ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Vascular Remodeling ◽  
Epoxide Hydrolase ◽  
Vascular Dysfunction ◽  
Soluble Epoxide Hydrolase ◽  
Protective Effects ◽  
Nicotine Treatment ◽  
Beneficial Effects ◽  
Sirt1 Inhibitor

Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2-/-) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide (NAM, SIRT1 inhibitor) simultaneously for four weeks. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2-/- mice without NAM treatment. However, the arterial protective effects were gone in Ephx2-/- mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced MMP2 upregulation via SIRT1-mediated YAP deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation.

scholarly journals Extraction, Chemical Composition, and Anticancer Potential of Origanum onites L. Essential Oil

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2612 ◽  
Author(s):  
Katerina Spyridopoulou ◽  
Eleni Fitsiou ◽  
Eleni Bouloukosta ◽  
Angeliki Tiptiri-Kourpeti ◽  
Manolis Vamvakias ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Essential Oil ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Biological Activities ◽  
Colorectal Cancer Cell Line ◽  
Ht 29 ◽  
Origanum Onites

Origanum species are plants rich in volatile oils that are mainly used for culinary purposes. In recent years, there has been a growing interest in the biological activities of their essential oils. Origanum onites L. is a plant mainly found in Greece, Turkey, and Sicily, whose oil is rich in carvacrol, a highly bioactive phytochemical. The aim of this study was to analyze the chemical composition of Origanum onites essential oil (OOEO), and investigate its potential anticancer effects in vitro and in vivo. GC/MS analysis identified carvacrol as OOEO’s main constituent. In vitro antiproliferative activity was assayed with the sulforhodamine B (SRB) assay against human cancer cell lines from four tumor types. HT-29, a colorectal cancer cell line, was the most sensitive to the antiproliferative activity of OOEO. Wound-healing assay and Annexin V-PI staining were employed to investigate the antimigratory and the pro-apoptotic potential of OOEO, respectively, against human (HT-29) and murine (CT26) colon cancer cells. Notably, OOEO attenuated migration and induced apoptosis-related morphological changes in both cell lines. Prophylactic oral administration of the oil in a BALB/c experimental mouse model inhibited the growth of syngeneic CT26 colon tumors. As far as we know, this is the first report on the antitumor potential of orally administered OOEO.

Synthesis of axially disubstituted silicon phthalocyanines and investigation of their in vitro cytotoxic/phototoxic anticancer activities

2020 ◽  
Vol 25 (01) ◽  
pp. 10-18
Author(s):  
Fatma Yurt ◽  
Ece Tugba Saka ◽  
Zekeriya Biyiklioglu ◽  
Ayça Tunçel ◽  
Derya Ozel ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Nuclear Imaging ◽  
Fibroblast Cell ◽  
Target Tissue ◽  
Anticancer Activities ◽  
Human Lung Fibroblast ◽  
Ht 29

In this study, two SiPcs have been selected and the photodynamic therapy potentials were evaluated of the Pcs. Synthesis of Axially 2-decyn-1-oxy disubstituted Es-SiPc-2 was newly synthesized by the reaction of SiPcCl2 with 2-decyn-1-ol in the presence of NaH in toluene. Furthermore, their nuclear imaging potentials were evaluated in human colon adenocarcinoma (HT-29) and human lung fibroblast cell (WI-38) cell lines. The uptake results have indicated that Es-SiPc labeled with [Formula: see text]I radionuclide ([Formula: see text]I-Es-SiPc) was approximately 2-fold higher in the HT-29 cell line than the WI-38 cell line. In other words, the target/non-target tissue ratio is defined as two in the HT-29/WI-38 cell lines. Besides, the uptake values of [Formula: see text]I-Es-SiPc were found to be higher than [Formula: see text]I-Es-SiPc-2. [Formula: see text]I-Es-SiPc and [Formula: see text]I-Es-SiPc-2 are promising for imaging or treating colon adenocarcinoma. In vitrophotodynamic therapy (PDT) studies have shown that both compounds are suitable and can be used in this field. Also, Es-SiPc has been shown to have higher phototoxicity than Es-SiPc-2.

scholarly journals Regulation of Ketogenic Enzyme HMGCS2 by Wnt/β-catenin/PPARγ Pathway in Intestinal Cells

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1106 ◽  
Author(s):  
Ji Tae Kim ◽  
Chang Li ◽  
Heidi L. Weiss ◽  
Yuning Zhou ◽  
Chunming Liu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Target Genes ◽  
Cancer Cell Lines ◽  
Intestinal Cell ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Human Colon Cancer ◽  
Intestinal Organoids

The Wnt/β-catenin pathway plays a crucial role in development and renewal of the intestinal epithelium. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting ketogenic enzyme in the synthesis of ketone body β-hydroxybutyrate (βHB), contributes to the regulation of intestinal cell differentiation. Here, we have shown that HMGCS2 is a novel target of Wnt/β-catenin/PPARγ signaling in intestinal epithelial cancer cell lines and normal intestinal organoids. Inhibition of the Wnt/β-catenin pathway resulted in increased protein and mRNA expression of HMGCS2 and βHB production in human colon cancer cell lines LS174T and Caco2. In addition, Wnt inhibition increased expression of PPARγ and its target genes, FABP2 and PLIN2, in these cells. Conversely, activation of Wnt/β-catenin signaling decreased protein and mRNA levels of HMGCS2, βHB production, and expression of PPARγ and its target genes in LS174T and Caco2 cells and mouse intestinal organoids. Moreover, inhibition of PPARγ reduced HMGCS2 expression and βHB production, while activation of PPARγ increased HMGCS2 expression and βHB synthesis. Furthermore, PPARγ bound the promoter of HMGCS2 and this binding was enhanced by β-catenin knockdown. Finally, we showed that HMGCS2 inhibited, while Wnt/β-catenin stimulated, glycolysis, which contributed to regulation of intestinal cell differentiation. Our results identified HMGCS2 as a downstream target of Wnt/β-catenin/PPARγ signaling in intestinal epithelial cells. Moreover, our findings suggest that Wnt/β-catenin/PPARγ signaling regulates intestinal cell differentiation, at least in part, through regulation of ketogenesis.

Sign in / Sign up

Export Citation Format

Share Document