scholarly journals AS-30D hepatoma as a model to study on insulin resistance in vitro.

2013 ◽  
Vol 60 (4) ◽  
Author(s):  
Katarzyna Wierzbicka-Bregier ◽  
Wojciech Brutkowski ◽  
Anna Borkowska ◽  
Krzysztof Milewski ◽  
Krzysztof Zabłocki
Keyword(s):  
Insulin Resistance ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Cellular Level ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatoma Cell Lines ◽  
Kinase Phosphorylation

Studies on insulin resistance of liver cells are often performed with the use of various hepatoma cell lines. Such an approach allows investigating selected biochemical pathways at the cellular level. However, possible modifications of metabolic processes due to the neoplastic nature of such cells must be considered. Expanding the diversity of hepatoma cell lines used in metabolic studies could deliver new data for comparison with those obtained for other cell lines and should reduce the risk of misleading conclusions. In this study rat hepatoma AS-30D cells were tested as a potential model for studies on palmitate-induced insulin resistance. It was found that insulin-induced Akt kinase phosphorylation was substantially reduced in cells incubated with palmitate at a concentration as low as 75 µM. This effect was not accompanied by excessive reactive oxygen species (ROS) generation or increased Jun N-terminal kinase (JNK) phosphorylation. Moreover, preincubation of AS-30D cells with rosiglitazone, an antidiabetic agonist of peroxisome proliferator-activated receptor gamma (PPARγ), efficiently prevented the palmitate-induced insulin resistance. We conclude that AS-30D hepatoma cells may be used as a model sensitive to insulin and vulnerable to palmitate-induced insulin resistance.

Non-genotoxic hepatocarcinogenesis in vitro: the FaO hepatoma line responds to peroxisome proliferators and retains the ability to undergo apoptosis

1993 ◽  
Vol 104 (2) ◽  
pp. 307-315 ◽  
Author(s):  
A.C. Bayly ◽  
N.J. French ◽  
C. Dive ◽  
R.A. Roberts
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferators ◽  
Hepatoma Cell Lines

A range of hepatoma cell lines (RH1, HTC, FaO, 7800C1 and MH1C1), has been studied with the aim of establishing an in vitro model to investigate the molecular mechanisms of hepatocarcinogenicity induced by the peroxisome proliferator class of non-genotoxic carcinogens. In view of speculation that peroxisome proliferators suppress hepatocyte apoptosis in vivo, we have placed particular emphasis on evaluating whether hepatoma cell lines retain the ability to undergo apoptotic cell death. Expression of the liver-specific differentiation marker albumin and the peroxisome proliferator-activated receptor (PPAR) was highest in the Reuber hepatoma cell line, FaO. This cell line also demonstrated the most marked response to the peroxisome proliferator nafenopin with a 2.2-fold induction of the microsomal enzyme cytochrome p450IVA1. This response was found to display intercellular heterogeneity by immunocytochemistry. Thus, the FaO cell line maintained characteristics of hepatocytes, both in vivo and in vitro, in terms of expression of constitutive and inducible markers. However, none of the cell lines tested mirrored the hyperplastic response of hepatocytes to nafenopin, since no increase in cell growth kinetics was observed on addition of nafenopin to the growth medium. The mode of cell death in confluent FaO cultures was characterised as apoptosis, by fluorescence microscopy and agarose gel electrophoresis of extracted DNA. Cells detaching from confluent FaO cultures exhibited chromatin condensation and DNA fragmentation patterns characteristic of cels undergoing apoptotic death.Interestingly, no apoptosis was seen in monolayer cells, suggesting that apoptosis in vitro is associated with cell shrinkage and detachment similar to that documented for the liver in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Distinct Regulation of Hepatitis B Virus Biosynthesis by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α and Small Heterodimer Partner in Human Hepatoma Cell Lines

2009 ◽  
Vol 83 (23) ◽  
pp. 12545-12551 ◽  
Author(s):  
Caitlin R. Ondracek ◽  
Vanessa C. Reese ◽  
Christel N. Rushing ◽  
Claudia E. Oropeza ◽  
Alan McLachlan
Keyword(s):  
Cell Lines ◽  
Nuclear Receptors ◽  
Hepatoma Cell ◽  
Peroxisome Proliferator ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatoma Cell Lines ◽  
Huh7 Cells ◽  
B Virus

ABSTRACT The human hepatoma cell lines HepG2 and Huh7 have been used extensively to study hepatitis B virus (HBV) transcription and replication. Both cell lines support transcription of the 3.5-kb viral pregenomic RNA and subsequent viral DNA synthesis by reverse transcription. The effects of the coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and corepressor small heterodimer partner (SHP) on HBV transcription and replication mediated by nuclear receptors were examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells in an attempt to determine the relative contribution of the various nuclear receptors to viral biosynthesis in the hepatoma cells. PGC1α and SHP modulated viral biosynthesis differently in the human hepatoma cell lines HepG2 and Huh7, indicating distinct modes of transcriptional regulation. Consistent with this suggestion, it appears that retinoid X receptor α/farnesoid X receptor α and liver receptor homolog 1 or estrogen-related receptor β (ERRβ) may contribute to the majority of the viral replication observed in HepG2 cells, whereas ERRα and ERRγ are probably responsible for the majority of viral biosynthesis in Huh7 cells. Therefore, this approach indicates that the transcriptional regulation of HBV biosynthesis in HepG2 and Huh7 cells is primarily controlled by different transcription factors.

Looking for synergy or additivity between 188Re and sorafenib on hepatoma cell lines.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 247-247
Author(s):  
Marc Pracht ◽  
Nicolas Lepareur ◽  
Julien Edeline ◽  
Laurence Lenoir ◽  
Valerie Ardisson ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cell ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
External Beam Radiotherapy ◽  
Combined Treatment ◽  
Hepatoma Cell Lines ◽  
Heparg Cell Line

247 Background: In case of non resectable HCC, radioembolization and sorafenib (S) are therapeutic options respectively for intermediate and advanced stages. In some other cancers, there is an increase of efficacy when external beam radiotherapy is done concomitantly with systemic chemotherapy or targeted therapies. So we wondered if there could be a synergistic or an additive activity when S is combined with a radionuclide. Methods: Hepatoma cell lines N1S1 (murine HCC), HepG2 (human hepatoblastoma) and HepaRG (human HCC) were treated with increasing concentrations of rhenium-188 (188Re) or S. On each cell line, we have studied the cellular toxicities of S and 188Re using Tetrazolium dye test, extra-cellular medium LDH level and morphologic analysis. This was done for different dosage of S and 188Re. We measured the lethal concentration killing 25% of cells (LC25) with the results of the Tetrazolium dye test. Secondly, we looked for synergy or additivity on cellular toxicity of these two compounds according to cell lines by combined treatment. Synergy or additivity was estimated with the combination index (CI) method (synergy if CI lower than 1, additivity if CI = 1, antagonism if CI upper to 1) based on the Tetrazolium dye test’s results. Results: Monotherapy dose-dependent toxicities were observed for all three cell lines with 188Re and for the N1S1 and HepG2 cell lines only with S. Combined treatment with 188Re and S showed synergy on HepaRG and N1S1 cell lines and additivity on the HepG2 cell line. Conclusions: The additive, and even synergistic, interest of a combined treatment with 188Re and S is demonstrated in vitro (for the first time to our knowledge) on hepatoma cell lines. This results, in particular for the HepaRG cell line (human HCC), could be explained by the down-regulation of the hepatic drug transporters which are responsible for the Sorafenib efflux in case of simultaneous DNA damages due to a radionuclide exposition. This promising approach now needs to be confirmed in vivo. [Table: see text]

Abstract 70: PPARdelta Agonist GW1516 Attenuates Diet-Induced Dyslipidemia, Insulin Resistance and Aortic Inflammation in Ldlr -/- Mice

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Lazar Bojic ◽  
Dawn Telford ◽  
Brian Sutherland ◽  
Cynthia Sawyez ◽  
Jane Edwards ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Er Stress ◽  
Proinflammatory Cytokines ◽  
Map Kinases ◽  
Fasting Blood Glucose ◽  
M2 Macrophage ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Arginase 1

Objective: The peroxisome proliferator-activated receptor (PPAR) delta has been implicated in systemic lipid homeostasis and inflammation. However, the role of PPARdelta agonists as anti-atherogenic agents remains unclear. In the present study, we used low-density lipoprotein receptor-null mice (Ldlr-/-) fed a high fat (HF) diet to test the hypothesis that a selective PPARdelta agonist corrects metabolic dysregulation and attenuates inflammation associated with atherosclerosis. Methods and Results: Ldlr -/- mice were fed chow or HF (42% fat, 0.2% cholesterol) for 4 weeks. Subsequently, the HF group was fed either HF or HF plus GW1516 (3mg/kg/d) for a further 8 weeks. Fasting plasma triglyceride, total cholesterol and free fatty acids were significantly decreased (-50%) by intervention with GW1516. In addition, GW1516 normalized fasting blood glucose and improved glucose and insulin tolerance. GW1516 also enhanced total energy expenditure compared to HF-fed mice. In the aorta, ER-stress markers CHOP and GRP78 were significantly elevated in HF-fed mice, which were markedly attenuated by GW1516-intervention. Aortae of HF-fed mice also showed marked elevations in the expression of proinflammatory cytokines including Ccl3, Il1beta, Icam1, Tnf, Il6 and Ccl2. Furthermore, HF-aortae, compared to chow, displayed reduced expression of the M2 macrophage marker arginase-1(Arg1). Intervention with GW1516 significantly attenuated aortic expression of all examined proinflammatory cytokines, and restored Arg1 expression. Enhanced MAPKerk signalling and decreased AKT/FoxO1 signalling are known to induce inflammatory cytokine expression in vitro. HF-feeding induced phosphorylation (p) of the MAP kinases ERK1/2 and p38 and dampened levels of pAKT and pFoxO1 in the aorta. In contrast, aortae of GW1516-treated animals displayed normalized levels of pERK1/2, p-p38, pAKT and pFoxO1. Conclusions: These studies demonstrate that PPARdelta activation ameliorates dyslipidemia and insulin resistance in HF-fed Ldlr -/- mice. Furthermore, PPARdelta activation inhibits aortic ER-stress as well as dysregulation of MAPK and AKT/FoxO1 signalling induced by HF-feeding, resulting in inhibition of the inflammatory response within the aorta.

Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies

2015 ◽  
Vol 30 (1) ◽  
pp. 331-340 ◽  
Author(s):  
A. Stampella ◽  
G. Rizzitelli ◽  
F. Donati ◽  
M. Mazzarino ◽  
X. de la Torre ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Hepatoma Cell Lines ◽  
Drug Drug Interaction ◽  
Gas Foaming
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