Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supernatant protein factor (SPF) is a recently cloned member of a family of cytosolic lipid-binding proteins that includes Sec14p, alpha-tocopherol transfer protein, and cellular retinal-binding protein. SPF stimulates the conversion of squalene to lanosterol in the downstream pathway for cholesterol biosynthesis, and overexpression of cloned SPF in hepatoma cells increases cholesterol synthesis. The mechanism of this stimulation has yet to be defined, but SPF appears to facilitate the transfer of squalene into and between intracellular membranes. The recent identification of SPF as alpha-tocopherol-associated protein (TAP) has called into question its long-standing association with cholesterol biosynthesis. TAP binds alpha-tocopherol, but not other isomers of tocopherol, with high affinity; in the presence of alpha-tocopherol TAP translocates to the nucleus and activates reporter gene transcription. Given the ability of alpha-tocopherol to down-regulate the expression of two scavenger lipoprotein receptors, SR-A and CD36, these observations raise some interesting questions regarding the role of SPF/TAP and vitamin E in cholesterol metabolism.
 ...
PMID:Supernatant protein factor and tocopherol-associated protein: an unexpected link between cholesterol synthesis and vitamin E (review). 1291 24

In certain tissues, glutathione biosynthesis is connected to methionine metabolism via the trans-sulfuration pathway. The latter condenses homocysteine and serine to cystathionine in a reaction catalyzed by cystathionine beta-synthase followed by cleavage of cystathionine to cysteine and alpha-ketoglutarate by gamma-cystathionase. Cysteine is the limiting amino acid in glutathione biosynthesis, and studies in our laboratory have shown that approximately 50% of the cysteine in glutathione is derived from homocysteine in human liver cells. In this study, we have examined the effect of pro- and antioxidants on the flux of homocysteine through the trans-sulfuration pathway in the human hepatoma cell line, HepG2. Our studies reveal that pyrrolidine dithiocarbamate and butylated hydroxyanisole enhance the flux of homocysteine through the trans-sulfuration pathway as has been observed previously with the pro-oxidants, H(2)O(2) and tertiary butyl hydroperoxide. In contrast, antioxidants such as catalase, superoxide dismutase and a water-soluble derivative of vitamin E elicit the opposite effect and result in diminished flux of homocysteine through the trans-sulfuration pathway. These studies provide the first evidence for the reciprocal sensitivity of the trans-sulfuration pathway to pro- and antioxidants, and demonstrate that the upstream half of the glutathione biosynthetic pathway (i.e. leading to cysteine biosynthesis) is redox sensitive as is the regulation of the well-studied enzymes in the downstream half (leading from cysteine to glutathione), namely, gamma-glutamyl-cysteine ligase and glutathione synthetase.
 ...
PMID:Redox regulation of homocysteine-dependent glutathione synthesis. 1263 46

To examine the effect of alpha-tocopherol(alpha-T), gamma-tocopherol(gamma-T), delta-tocopherol(delta-T), and vitamin E succinate (VES) on the proliferation of human hepatoma cell (HepG2), cell proliferation was detected by hemocytometer count, MTT assay and flow cytometry (FCM) with different VE homologues analogues (alpha-T, gamma-T, delta-T and VES) and different concentrations (12.5 mg/L, 25 mg/L, 50 mg/L, 100 mg/L and 200 mg/L). The results showed that The growth of HepG2 cells was inhibited by delta-T and VES at the dosages of 12.5-200 mg/L in comparison with the negative control group, while gamma-T showed weak effect of inhibition and alpha-T did not show any inhibition effect. The dose range to produce inhibition effects varied with different analogues. A dose-dependent inhibition of cell growth was found in HepG2 cell lines treated with different vitamin E homologues analogues. An accumulation of cells in G0/G1-phase and a significant decreasing of cells in S-phase were found as evaluated by flow cytometric analysis employing a PI-staining method. It is suggested that delta-tocopherol and VES decreased HepG2 cells growth and viability. A dose-dependent of anti-proliferation was found in HepG2 cells line. the order of efficiency of four vitamin E analogues was delta-tocopherol > VES > gamma-tocopherol > alpha-tocopherol. The proliferation was blocked in S-phase. The difference in nature and magnitude of the anticancer effects does not correlate with their reported relative antioxidant activity and might be due to minor differences in their structure important to their biological activities. These results suggest that delta-tocopherol and VES could be promising anti-hepatoma agents.
 ...
PMID:[Effect of different vitamin E homologous analogues on human hepatoma cell HepG2 proliferation in vitro]. 1273 Dec 85

The aim of this study was to determine the effects of vitamin E (alpha-tocopherol) on the low density lipoprotein (LDL) receptor, a cell surface protein which plays an important role in controlling blood cholesterol. Human HepG2 hepatoma cells were incubated for 24 hours with increasing amounts of alpha, delta, or gamma-tocopherol. The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA, cell cholesterol and cell lathosterol were measured. The effect of alpha-tocopherol was biphasic. Up to a concentration of 50 microM, alpha-tocopherol progressively increased LDL receptor binding activity, protein and mRNA to maximum levels 2, 4 and 6-fold higher than control, respectively. The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 microM alpha-tocopherol. The cell cholesterol concentration was decreased by 20% compared to control at 50 microM alpha-tocopherol. However, at alpha-tocopherol concentrations higher than 50 microM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. The biphasic effect on the LDL receptor was specific for alpha-tocopherol in that delta and gamma-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. In conclusion, alpha-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. Cholesterol synthesis appears to be similarly affected and the cell cholesterol concentration may mediate these effects.
 ...
PMID:Alpha-tocopherol modulates the low density lipoprotein receptor of human HepG2 cells. 1277 5

To observe the effect of alpha-tocopherol(gamma-T), delta-tocopherol(delta-T), delta-tocopherol(delta-T), and vitamin E succinate (VES) on apoptosis induced in human hepatoma cells (HepG2), the cell apoptosis was detected by flow cytometry (FCM) and DNA ladder under the treatment of different VE homologues analogues (alpha-T, gamma-T, delta-T and VES) at different concentrations (12.5, 25, 50, 100 and 200 mg/L) for 48 hours. The results showed that the growth of HepG2 cells was inhibited by delta-T and VES at 12.5-200 mg/L in comparison with the negative control group, while gamma-T showed weak effect of inhibition and alpha-T did not show any inhibition effect. With the exception of alpha-tocopherol, delta-tocopherol and VES were effective in induction of apoptosis in HepG2 cells at concentrations of 12.5-200 mg/L. gamma-tocopherol showed effect only at 200 mg/L. delta-tocopherol and VES decreased HepG2 cells growth and viability, and increased apoptotic propensity significantly. A dose-dependent of antiproliferation and induction of apoptosis were found in HepG2 cells line. The order of efficiency of four vitamin E analogues was delta-tocopherol > VES > gamma-tocopherol > alpha-tocopherol. It is suggested that delta-tocopherol and VES may be a agent that has a anti-hepatomatic potential.
 ...
PMID:[Effect of apoptosis induced by different vitamin E homologous analogues in human hepatoma cells (HepG2)]. 1279 4

To observe the effect of apoptosis induced by alpha-tocopherol(alpha-T), gamma-tocopherol(gamma-T), delta-tocopherol(delta-T), and vitamin E succinate (VES) in human hepatoma cells (HepG2), apoptosis was detected by flow cytometry (FCM) and DNA ladder with different VE homologues analogues (alpha-T, gamma-T, delta-T and VES) and different concentrations (12.5 mg/L, 25 mg/L, 50 mg/L, 100 mg/L and 200 mg/L) at 48 h. The growth of HepG2 cells was inhibited by delta-T and VES at 12.5-200 mg/L in comparison with the negative control group, while (-T showed weak effect of inhibition and alpha-T did not show any inhibition effect. However, as an exception, alpha-tocopherol, delta-tocopherol and VES were effective in induction of apoptosis in HepG2 cells at concentrations of 12.5-200 mg/L. gamma-tocopherol showed effect only at 200 mg/L. Conclusions delta-tocopherol and VES lowered HepG2 cells growth and viability, and increased apoptotic propensity significantly. A dose-dependent of antiproliferation and induction apoptosis was found in HepG2 cells line. The order of efficiency of four vitamin E analogues was delta-tocopherol > VES > gamma-tocopherol > alpha-tocopherol. The difference in nature and magnitude of the anticancer effects did not correlate with their reported antioxidant activity and this might be due to minor differences in their structure important to their biological activities. The results from this study suggested that delta-tocopherol and VES could be the promising anti-hepatoma agents.
 ...
PMID:[Effect of apoptosis induced by different vitamin E homologous analogues in human hepatoma cells(HepG2)]. 1453 97

Growth factor deprivation-induced apoptosis has been shown in various cell systems and is recognized as one of the standard models for the study of programmed cell death. The mechanism of induction of apoptosis by serum deprivation is still not clear. The objective of the present study was to investigate if serum-deprivation causes oxidative stress, which then leads to apoptotic death. We have demonstrated that indeed, there was a significant increase in reactive oxygen species following serum deprivation of 5123tc hepatoma cells. Furthermore, treatment with anti-oxidants; melatonin or vitamin E, prevented cell death caused by serum-deprivation. We also demonstrated that there was activation of proteasome proteases and decrease in glutathione levels following serum deprivation. Interestingly, melatonin treatment blocked these changes and rescued the cells from apoptosis induced by serum-deprivation. These results indicated that oxidative stress may play a causal role in the induction of apoptosis induced by serum deprivation.
 ...
PMID:Oxidative stress and activation of proteasome protease during serum deprivation-induced apoptosis in rat hepatoma cells; inhibition of cell death by melatonin. 1460 56

Physalis angulata and P. peruviana are herbs widely used in folk medicine. In this study, the aqueous and ethanol extracts prepared from the whole plant of these species were evaluated for their antihepatoma activity. Using XTT assay, three human hepatoma cells, namely Hep G2, Hep 3B and PLC/PRF/5 were tested. The results showed that ethanol extract of P. peruviana (EEPP) possessed the lowest IC50 value against the Hep G2 cells. Interestingly, all extracts showed no cytotoxic effect on normal mouse liver cells. Treatment with carbonyl cyanide m-chlorophenyl hydrazone, a protonophore, caused a reduction of membrane potential (Deltapsim) by mitochondrial membrane depolarization. At high concentrations, EEPP was shown to induce cell cycle arrest and apoptosis through mitochondrial dysfunction as demonstrated by the following observations: (i) EEPP induced the collapse of Deltapsim and the depletion of glutathione content in a dose dependent manner; (ii) pretreatment with the antioxidant (1.0 microg/ml vitamin E) protected cells from EEPP-induced release of ROS; and (iii) at concentrations 10 to 50 microg/ml, EEPP displayed a dose-dependent accumulation of the Sub-G1 peak (hypoploid) and caused G0/G1-phase arrest. Apoptosis was elicited when the cells were treated with 50 microg/ml EEPP as characterized by the appearance of phosphatidylserine on the outer surface of the plasma membrane. The results conclude that EEPP possesses potent antihepatoma activity and its effect on apoptosis is associated with mitochondrial dysfunction.
 ...
PMID:Antihepatoma activity of Physalis angulata and P. peruviana extracts and their effects on apoptosis in human Hep G2 cells. 1496

Epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx and the oesophagus and of the liver. The increased risk attributable to alcohol consumption of cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumours, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers is controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen but under certain experimental conditions is a cocarcinogen and/or tumour promoter. The metabolism of ethanol leads to the generation of acetaldehyde (AA) and free radicals. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, destructs folate and results in secondary hyperproliferation. Acetaldehyde is produced by tissue alcohol hydrogenases, cytochrome P 4502E1 and through bacterial oxidative metabolism in the upper and lower gastrointestinal tract. Its generation or its degradation is modulated due to functional polymorphisms of the genes coding for the enzymes. Acetaldehyde can also be produced by oral and faecal bacteria. Smoking, which changes the oral bacterial flora, and poor oral hygiene also increase acetaldehyde. In addition, cigarette smoking and some alcoholic beverages such as calvados contain acetaldehyde. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P-4502E1, which is associated with an enhanced production of free radicals and enhanced activation of various procarcinogens present in alcoholic beverages; in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens; alterations in cell cycle behaviour such as cell cycle duration leading to hyperproliferation; nutritional deficiencies, such as methyl-, vitamin E-, folate-, pyridoxal phosphate-, zinc- and selenium deficiencies and alterations of the immune system eventually resulting in an increased susceptibility to certain virus infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Also, an alcohol-mediated increase in oestradiols may be at least in part responsible for breast cancer risk. Thus, all these mechanisms functioning in concert actively modulate carcinogenesis leading to its stimulation.
 ...
PMID:Alcohol and cancer. 1508 51

How omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) lower plasma lipid levels is incompletely understood. We previously showed that marine omega-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid) stimulate a novel pathway, post-ER presecretory proteolysis (PERPP), that degrades apolipoprotein B100 (ApoB100), thereby reducing lipoprotein secretion from liver cells. To identify signals stimulating PERPP, we examined known actions of omega-3 PUFA. In rat hepatoma or primary rodent hepatocytes incubated with omega-3 PUFA, cotreatment with the iron chelator desferrioxamine, an inhibitor of iron-dependent lipid peroxidation, or vitamin E, a lipid antioxidant, suppressed increases in thiobarbituric acid-reactive substances (TBARSs; a measure of lipid peroxidation products) and restored ApoB100 recovery and VLDL secretion. Moreover, omega-6 and nonmarine omega-3 PUFA, also prone to peroxidation, increased ApoB100 degradation via intracellular induction of TBARSs. Even without added fatty acids, degradation of ApoB100 in primary hepatocytes was blocked by desferrioxamine or antioxidant cotreatment. To extend these results in vivo, mice were infused with DHA, which increased hepatic TBARSs and reduced VLDL-ApoB100 secretion. These results establish a novel link between lipid peroxidation and oxidant stress with ApoB100 degradation via PERPP, and may be relevant to the hypolipidemic actions of dietary PUFAs, the basal regulation of ApoB100 secretion, and hyperlipidemias arising from ApoB100 overproduction.
 ...
PMID:Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production. 1512 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>