Cytotoxic Effect of Peroxisome Proliferator Fenofibrate on Human HepG2 Hepatoma Cell Line and Relevant Mechanisms

2002 ◽  
Vol 185 (3) ◽  
pp. 172-179 ◽  
Author(s):  
H Jiao
Life Sciences ◽  
2010 ◽  
Vol 86 (1-2) ◽  
pp. 10-16 ◽  
Author(s):  
Meng Li ◽  
Fei Chen ◽  
Cui-Ping Liu ◽  
Dong-Mei Li ◽  
Xiang Li ◽  
...  

1994 ◽  
Vol 125 (1) ◽  
pp. 197-203 ◽  
Author(s):  
A C Bayly ◽  
R A Roberts ◽  
C Dive

Suppression of apoptosis has been implicated as a mechanism for the hepatocarcinogenicity of the peroxisome proliferator class of non-genotoxic carcinogens. The ability of the peroxisome proliferator nafenopin to suppress or delay the onset of liver apoptosis was investigated using primary cultures of rat hepatocytes and the Reuber hepatoma cell line FaO. 50 microM nafenopin reversibly maintained the viability of primary rat hepatocyte cultures which otherwise degenerated within 8 d of establishment. The maintenance of viability of hepatocyte monolayers was associated with a significant decrease in the number of cells exhibiting chromatin condensation patterns typical of apoptosis. Apoptosis could be induced in hepatocytes by administration of 5 ng/ml TGF beta 1. Co-addition of 50 microM nafenopin significantly reduced TGF beta 1-induced apoptosis by 50-60%. TGF beta 1 (1-5 ng/ml) also induced apoptosis in the FaO rat hepatoma cell line. Cell death was accompanied by detachment of FaO cells from the monolayer and detached cells exhibited chromatin condensation and non-random DNA fragmentation patterns typical of apoptosis. Co-addition of 50 microM nafenopin to TGF beta 1-treated FaO cultures significantly reduced the number of apoptotic cells detaching from the monolayer at 24 h. In contrast, nafenopin had no significant effect on FaO apoptosis induced by the DNA damaging agents etoposide and hydroxyurea. We conclude that suppression of liver cell death by apoptosis may play a role in the hepatocarcinogenicity of the peroxisome proliferators, although the extent of this protection is dependent on the nature of the apoptotic stimulus.


2011 ◽  
Vol 672 (1-3) ◽  
pp. 113-120 ◽  
Author(s):  
Qing-Ping Zuo ◽  
Shi-Kun Liu ◽  
Zuo-Jun Li ◽  
Bing Li ◽  
Yu-Lu Zhou ◽  
...  

1993 ◽  
Vol 104 (2) ◽  
pp. 307-315 ◽  
Author(s):  
A.C. Bayly ◽  
N.J. French ◽  
C. Dive ◽  
R.A. Roberts

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)


Open Biology ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 180147 ◽  
Author(s):  
Stephanie Sefried ◽  
Hans-Ulrich Häring ◽  
Cora Weigert ◽  
Sabine S. Eckstein

Immortal hepatocyte cell lines are widely used to elucidate insulin-dependent signalling pathways and regulation of hepatic metabolism, although the often tumorigenic origin might not represent the metabolic state of healthy hepatocytes. We aimed to investigate if murine cell line AML12 and human cell line THLE-2, which are derived from healthy liver cells, are comparable to hepatoma cell line HepG2 for studying acute insulin signalling and expression of gluconeogenic enzymes and hepatokines. Insulin responsiveness of AML12 and THLE-2 cells was impaired when cells were cultured in the recommended growth medium, but comparable with HepG2 cells by using insulin-deficient medium. THLE-2 cells showed low abundance of insulin receptor, while protein levels in HepG2 and AML12 were comparable. AML12 and THLE-2 cells showed only low or non-detectable transcript levels of G6PC and PCK1 . Expression of ANGPTL4 was regulated similarly in HepG2 and AML12 cells upon peroxisome proliferator-activated receptor δ activation but only HepG2 cells resemble the in vivo regulation of hepatic ANGPTL4 by cAMP. Composition of the culture medium and protein expression levels of key signalling proteins should be considered when AML12 and THLE-2 are used to study insulin signalling. With regard to gluconeogenesis and hepatokine expression, HepG2 cells appear to be closer to the in vivo situation despite the tumorigenic origin.


2006 ◽  
Vol 9 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Hyun Joo Woo ◽  
Kun-Young Park ◽  
Chung-Ho Rhu ◽  
Won Ho Lee ◽  
Byung Tae Choi ◽  
...  

2011 ◽  
Vol 252 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Rong Zhang ◽  
Jianguo Sun ◽  
Liping Ma ◽  
Xiaolan Wu ◽  
Guoyu Pan ◽  
...  

Author(s):  
Nora A. Bawazeer ◽  
Hani Choudary ◽  
Mazin A. Zamzami ◽  
Wesam H. Abdulaal ◽  
Mustafa Zeyadi ◽  
...  

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