Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2

2006 ◽  
Vol 84 (1) ◽  
pp. 102-111 ◽  
Author(s):  
Monica P Polo ◽  
Margarita G de Bravo
Keyword(s):  
Fatty Acid ◽  
Cell Line ◽  
Reductase Activity ◽  
Hepatoma Cell ◽  
Cellular Growth ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Hep G2 ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor activity against several cell lines. We have studied the effects of geraniol on growth, fatty-acid metabolism, and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 µmol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase activity of these cells. At the same concentrations, it increased the incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol-treated cells incorporated less 14C-acetate into nonsaponifiable lipids, inhibiting its incorporation into cholesterol but not into squalene and lanosterol. This is indicative of an inhibition in cholesterol synthesis at a step between lanosterol and cholesterol, a fact confirmed when cells were incubated with 3H-mevalonate. The incorporation of 3H-mevalonate into protein was also inhibited, whereas its incorporation into fatty acid increased. An inhibition of Δ5 desaturase activity was demonstrated by the inhibition of the conversion of 14C-dihomo-γ-linolenic acid into arachidonic acid. Geraniol has multiple effects on mevalonate and lipid metabolism in Hep G2 cells, affecting cell proliferation. Although mevalonate depletion is not responsible for cellular growth, it affects cholesterogenesis, protein prenylation, and fatty-acid metabolism.Key words: geraniol, Hep G2, HMG-CoA reductase, mevalonate, fatty acids.

scholarly journals Effects of compactin, mevalonate and low-density lipoprotein on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and low-density-lipoprotein-receptor activity in the human hepatoma cell line Hep G2

1984 ◽  
Vol 222 (1) ◽  
pp. 35-39 ◽  
Author(s):  
L H Cohen ◽  
M Griffioen ◽  
L Havekes ◽  
D Schouten ◽  
V van Hinsbergh ◽  
...  
Keyword(s):  
Reductase Activity ◽  
Hepatoma Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatoma Cell Line ◽  
Low Density ◽  
Hep G2 ◽  
Human Hepatoma Cell ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Compactin, an inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, decreased cholesterol synthesis in intact Hep G2 cells. However, after the inhibitor was washed away, the HMG-CoA-reductase activity determined in the cell homogenate was found to be increased. Also the high-affinity association of LDL (low-density lipoprotein) to Hep G2 cells was elevated after incubation with compactin. Lipoprotein-depleted serum, present in the incubation medium, potentiated the compactin effect compared with incubation in the presence of human serum albumin. Addition of either mevalonate or LDL prevented the compactin-induced rise in activities of both HMG-CoA reductase and LDL receptor in a comparable manner. It is concluded that in this human hepatoma cell line, as in non-transformed cells, both endogenous mevalonate or mevalonate-derived products and exogenous cholesterol are able to modulate the HMG-CoA reductase activity as well as the LDL-receptor activity.

scholarly journals Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA contents in human hepatoma cell line Hep G2 by distinct classes of mevalonate-derived metabolites

1988 ◽  
Vol 255 (1) ◽  
pp. 61-67 ◽  
Author(s):  
L H Cohen ◽  
M Griffioen
Keyword(s):  
Reductase Activity ◽  
Hepatoma Cell ◽  
Enzyme Level ◽  
Mrna Level ◽  
Hepatoma Cell Line ◽  
Hep G2 ◽  
Hmg Coa Reductase ◽  
Mrna Content ◽  
Reductase Mrna ◽  
Coa Reductase

Hep G2 cells were incubated under conditions known to influence the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity, e.g. in the presence of compactin (a competitive inhibitor of HMG-CoA reductase itself) and U18666A (a squalene-2,3-epoxide cyclase inhibitor). We studied the effects of these conditions both on the HMG-CoA reductase activity and on the reductase mRNA content. In the presence of compactin the mRNA content increased, but less than the enzyme activity, as determined after removal of the inhibitor. The increase in mRNA could be prevented by addition of mevalonate or by a combination of low-density lipoprotein (LDL) plus a low concentration of mevalonate. LDL alone prevented the compactin-induced increases in mRNA and activity only partially. The effect of U18666A on reductase mRNA content and activity was biphasic, i.e. a slight decrease at low (0.3-0.5 microM) concentrations, with a concomitant formation of polar sterols [Boogaard, Griffioen & Cohen (1987) Biochem. J. 241, 345-351], and an increase at high (20-30 microM) concentrations, with complete blockage of sterol formation. At these high concentrations of U18666A, additional compactin (2 microM) increased the reductase activity, but not the mRNA content. We conclude that non-sterol metabolites of mevalonate regulate exclusively at the enzyme level, whereas sterol metabolites regulate at the reductase mRNA level. In the latter group of regulators we distinguish mevalonate metabolites which can, and metabolites which cannot, be replaced by exogenous LDL.

Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells

1985 ◽  
Vol 110 (2) ◽  
pp. 200-206 ◽  
Author(s):  
P. W. Johansen ◽  
E. Haug ◽  
K. M. Gautvik
Keyword(s):  
Cell Line ◽  
Hepatoma Cell ◽  
Cellular Growth ◽  
Maximum Effect ◽  
Epithelial Cell Line ◽  
Hepatoma Cell Line ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Hormone Production ◽  
Rat Pituitary

Abstract. Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 × 10−5 mol/l), a dopamine (DA) agonist, induced a rapid reduction in Prl and GH secretion with maximum effect (approximately 60%) after 15 min of treatment. Bromocriptine also inhibited Prl and GH production in a time- and dose-dependent manner with ED50 at 4 × 10−6 mol/l and 7 × 10−6 mol/l, respectively. Maximum effect was obtained at 5 × 10−5 mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by ∼ 70 and ∼ 50%, respectively. After 9 days of treatment both Prl and GH production was reduced by more than 95%. Bromocriptine also reduced cellular growth rate. The ED50 was ∼ 1 × 10−5 mol/l and the maximum effect (> 50%) was observed at 5 × 10−5 mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The anti-proliferative effect of bromocriptine was also observed using a rat hepatoma cell line (MH1C1) and a human epithelial cell line (HE), suggesting a non-receptor mediated growth inhibition at high concentrations of the drug. In conclusion, the inhibitory effect of bromocriptine on secretion and production of both Prl and GH in GH3 cells occurs at a lower concentration than its effect on cell proliferation. The pharmacological effects of bromocriptine in vivo on Prl and GH producing adenomas may be explained by an action directly at the pituitary level.

scholarly journals Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in human hepatoma cell line Hep G2. Effects of inhibitors of cholesterol synthesis on enzyme activity

1987 ◽  
Vol 241 (2) ◽  
pp. 345-351 ◽  
Author(s):  
A Boogaard ◽  
M Griffioen ◽  
L H Cohen
Keyword(s):  
Coenzyme A ◽  
Reductase Activity ◽  
Hepatoma Cell ◽  
Lipid Fraction ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Hep G2 ◽  
Human Hepatoma Cell ◽  
Sites Of Action ◽  
Coenzyme A Reductase

Incubating Hep G2 cells for 18 h with triparanol, buthiobate and low concentrations (less than 0.5 microM) of U18666A, inhibitors of desmosterol delta 24-reductase, of lanosterol 14 alpha-demethylase and of squalene-2,3-epoxide cyclase (EC 5.4.99.7) respectively, resulted in a decrease of the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activity. However, U18666A at concentrations higher than 3 microM increased the HMG-CoA reductase activity in a concentration-dependent manner. None of these inhibitors influenced directly the reductase activity in Hep G2 cell homogenates. Analysis by t.l.c. of 14C-labelled non-saponifiable lipids formed from either [14C]acetate or [14C]mevalonate during the cell incubations confirmed the sites of action of the drugs used. Beside the 14C-labelled substrates of the blocked enzymes and 14C-labelled cholesterol, another non-saponifiable lipid fraction was observed, which behaves as polar sterols on t.l.c. This was the case with triparanol and at those concentrations of U18666A that decreased the reductase activity, suggesting that polar sterols may play a role in suppressing the reductase activity. In the presence of 30 microM-U18666A (sterol formation blocked) the increase produced by simultaneously added compactin could be prevented by addition of mevalonate. This indicates the existence of a non-sterol mevalonate-derived effector in addition to a sterol-dependent regulation. LDL (low-density lipoprotein), which was shown to be able to decrease the compactin-induced increase in reductase activity, could not prevent the U18666A-induced increase. On the contrary, LDL enhanced the U18666A effect, showing that the LDL regulation is not merely the result of introducing cholesterol to the cells.

Ecological and physiological as well as biochemical properties of representatives of the Genus sedum L.

2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko
Keyword(s):  
Nitric Oxide ◽  
Cell Line ◽  
Methanol Extract ◽  
Hepatoma Cell ◽  
Ethanol Extract ◽  
Biochemical Properties ◽  
Biologically Active ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Dose Dependent

The article deals with the history of the study and the current state of research of physiological and biochemical properties of the plant genus Sedum that are useful for human and has been used in folk medicine for many years. It was noticed that antioxidant properties of extracts from plants S. sarmentosum, S. sempervivoides, S. takesimense were caused by the presence of phenolic compounds. Methanol extract of plants S. takesimense exhibited strong scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals as well as significant inhibitory effects on lipid peroxidation and low density lipoprotein (LDL) oxidation induced by a metal ion Cu2+. Various immunomodulatory activities of various fractions of plants extracts (S. dendroideum, S. kamtschaticum, S. sarmentosum, S. telephium) are observed. It was shown that the ethanol extract of S. sarmentosum and it’s fractions suppressed specific antibody and cellular responses to ovalbumin in mice. The methanol extract of plants S. sarmentosum reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes, suppressed nitric oxide synthesis in activated macrophages via suppressed induction of inducible nitric oxide synthase (iNOS). Polysaccharides fractions from plants S. telephium inducing productions of tumor necrosis factor alpha (TNF-α), increasing the intensity of phagocytosis in vitro and in vivo. Methanol extract from the whole part of S. kamtschaticum strongly inhibit PGE2 production from lipopolysaccharide-induced RAW 264.7 cells, a mouse macrophage cell line via modulating activity in gene expression of the enzyme cyclooxygenase-2 (COX-2). The methanol extract of plants S. sarmentosum and the major kaempferol glycosides from S. dendroideum have antinociceptive activity. It was noticed that anti-adipogenic activity of extracts from plants S. kamtschaticum were caused by inhibition of peroxisome-proliferator-activated receptor γ (PPARγ) expression and it’s dependent target genes, such as genes encoding adipocyte protein 2 (аР2), lipoprotein lipase (LPL), adiponectin and CD36. Polysaccharides fractions from S. telephium cause inhibition of cell adhesion of human fibroblast (MRC5) to laminin and fibronectin via interfere with integrin-mediated cell behaviour and they contributed to the role of polysaccharides in cell-matrix interaction. The methanol extract of plants S. sarmentosum exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane angiogenesis in a dose-dependent manner. The crude alkaloid fraction of S. sarmentosum caused a dose-dependent inhibition of cell proliferation on murine hepatoma cell line BNL CL.2 and human hepatoma cell line HepG2 without necrosis or apoptosis. Alkaloids from plants S. sarmentosum may improve survival of hepatoma patients via the inhibition of excessive growth of tumor cells. Plant’s juices have antiviral activity (S. sarmentosum, S. spurium, S. stahlii). Crude ethanol extract S. praealtum have spermicidal activity of the in mice and a relevant inhibitory effect of aqueous extract on human spermatozoa motility as well as an anti-fertilizing activity in rats. Hepatoprotective triterpenes, e.g., δ-amyrone, 3-epi-δ-amyrin, δ-amyrin and sarmentolin were isolated from S. sarmentosum. 2- and 2,6-substituted piperidine alkaloids (e.g., norsedamine, allosedridine, sedamine, allosedamine) are observed in plants S. acre, which in the presence of data on the use of pyridine and piperidine derivatives for treating neurodegenerative diseases (e.g., Alzheimer's disease), points on the promising research in this area. Taking into account that biologically active compounds are accumulated in the aboveground vegetative organs of plants of Sedum, the prospects of further study of the use of Sedum for the purposes of biotechnology and in the pharmaceutical industry becomes apparent. This work extends the existing views regarding the use of plants Sedum.

Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line

1989 ◽  
Vol 257 (5) ◽  
pp. C888-C895 ◽  
Author(s):  
E. Coezy ◽  
I. Darby ◽  
J. Mizrahi ◽  
B. Cantau ◽  
M. H. Donnadieu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Ang Ii ◽  
Hep G2 ◽  
Dose Dependent

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.

Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human liver HepG2 and L02 cells

2018 ◽  
Vol 37 (12) ◽  
pp. 1293-1309 ◽  
Author(s):  
Y Xue ◽  
J Wang ◽  
Y Huang ◽  
X Gao ◽  
L Kong ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Hepatoma Cell ◽  
Death Receptor ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Death Receptor Pathway ◽  
L02 Cells

Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20–160 μg mL−1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.

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