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

Albumin carries fatty acids and has also been suggested to act as an antioxidant. In the present work, polyunsaturated fatty acids (linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acids)--but not palmitic and oleic acid--inhibited growth of human hepatoma cells in low albumin concentration (0.5%). Growth inhibition by polyunsaturated fatty acids was prevented by albumin in a dose-related manner in the range 0.7-5.0%. Albumin also protected against growth inhibition following catabolism (by lipoprotein lipase) of very low density lipoproteins. Vitamin E strongly counteracted the inhibitory effect of polyunsaturated fatty acids. Vitamin E and albumin appeared to have additive effects in protecting against growth inhibition by polyunsaturated fatty acids. Indomethacin did not greatly modify the polyunsaturated fatty acids effect. Growth inhibition by polyunsaturated fatty acids, as well as the level of thiobarbituric acid reacting substances (a measure of lipid peroxidation) in growth media, increased with increasing number of fatty acids double bonds. Vitamin E and albumin prevented both thiobarbituric acid reacting substances formation and growth inhibition by polyunsaturated fatty acids. The results suggest that the concentrations of albumin and vitamin E in the incubation medium are essential when studying polyunsaturated fatty acids effects on cell growth.
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PMID:Growth inhibition of human hepatoma cells (HepG2) by polyunsaturated fatty acids. Protection by albumin and vitamin E. 131 55

Measurements of the absolute rate constants for the reaction with peroxyl radicals of alpha, beta, gamma and delta-tocopherol and several model compounds are described. The peroxyl radicals were obtained either by the autoxidation of styrene or by the flash photolysis of di-t-butyl ketone in an oxygen-saturated environment. The kinetic data are discussed in stereoelectronic terms. Vitamin E and total lipid-soluble, chain-breaking antioxidant concentrations in some normal and cancerous tissues have been measured. In human blood plasma and erythrocyte ghost membranes vitamin E is the major, and possibly the only, chain-breaking antioxidant. Lipid extracts of Novikoff ascites hepatoma cells contain considerably more vitamin E relative to lipid than do extracts of normal rat liver. These tumour lipids contain relatively fewer highly unsaturated fatty acids and are present at lower lipid/wet tissue ratios than the normal liver lipids. A number of unresolved problems relating to the action of vitamin E in vivo are discussed.
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PMID:Vitamin E as an antioxidant in vitro and in vivo. 655 6

The protective influence of bovine serum albumin against growth inhibition caused by fatty acids was studied in human hepatoma (HepG2) and immortalized human kidney epithelial (IHKE) cells. In general, growth inhibition by unsaturated fatty acids (0.15 mmol/liter) increased with increasing number of double bonds. For HepG2 cells crude albumin (1 g/100 ml) did not greatly modify growth inhibition by arachidonic, eicosapentaenoic, and docosahexaenoic acid. With oleic, linoleic, and linolenic acids, crude and defatted albumin stimulated cell growth. In contrast, for IHKE cells both albumins counteracted growth inhibition by unsaturated fatty acids to approximately the same extent. When HepG2 cells were cultured in the presence of saturated fatty acids (0.3 mmol/liter), C2, C6, and C8 had no or little inhibitory effect. C10 and C12 inhibited cell growth appreciably, whereas C14, and especially C16, had poor inhibitory effects. Crude albumin counteracted growth inhibition by all these fatty acids. In contrast, defatted albumin had little or no effect (except against C10 and C12), and even increased the growth inhibition by C14 and C16. With unsaturated fatty acids there seemed to be an inverse relationship between cell growth and the concentration of thiobarbituric acid reactive substances (TBARS) in media. Vitamin E abolished growth inhibition (and the increase in TBARS concentration) by unsaturated fatty acids. The complex interaction between fatty acids and albumins calls for great caution when interpreting data on growth effects.
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PMID:Influence of fatty acids and bovine serum albumin on the growth of human hepatoma and immortalized human kidney epithelial cells. 782 Mar 6

A case-control study was carried out in 59 patients with newly diagnosed hepatocellular carcinoma and 101 control subjects, who were all male hepatitis B carriers. The odds ratios of hepatocellular carcinoma occurring among hepatitis B carriers in the lowest quartile and those highest quartile of dietary and serum status were 5.3 (1.9 to 15.0) and 86.9 (20.0 to 377.2), respectively. The odds ratios for hepatitis B carriers in the lowest quartile and those in the highest quartile of dietary and serum beta-carotene status were 1.7 (0.7 to 4.1) and 5.0 (1.9 to 13.2). Vitamin E status did not differ in case patients and control subjects. Low education level, heavy consumption of alcohol, and smoking status were also associated with increased odds of hepatocellular carcinoma. Serum retinol, positively associated with dietary retinol, demonstrated an independent effect on hepatocellular carcinoma. This effect may reflect changes in the physiologic condition of the patients at the time of entering the hospital.
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PMID:Vitamin A, Vitamin E or beta-carotene status and hepatitis B-related hepatocellular carcinoma. 827 92

Effect of glutathione (GSH) depletion on paraquat (PQ) toxicity in the liver and kidneys of mice was examined. Glutamic-pyruvate transaminase (GPT) and blood urea nitrogen (BUN) levels in plasma of mice were hardly changed by treatment with 150 micro mol/kg of PQ. However, significant increases in the plasma GPT and BUN levels after PQ injection were observed in mice which were pretreated with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, at 4 hr prior to PQ administration. This result supports the previous observation that hepatotoxicity of PQ was enhanced in diethyl maleate-pretreated mice (Cagen and Gibson, 1977). In the present study, lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBA-RS) level in the liver of mice given PQ was elevated by pretreatment with BSO. Moreover, enhancement of PQ cytotoxicity by BSO pretreatment was also observed in cultured mouse hepatoma cell line (NCTC clone 1469). Vitamin E, an antioxidant, and Desferal, an iron chelator, significantly prevented mice from the BSO-enhanced hepato- and nephrotoxicity of PQ. These findings suggest that the tissues or cells of low GSH concentration are highly vulnerable to PQ toxicity and GSH may play a major role in diminishing the toxic action of PQ exerted through oxidative stress.
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PMID:Enhancement of paraquat toxicity by glutathione depletion in mice in vivo and in vitro. 872 Jan 62

Vitamin E (alpha-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. alpha-Tocopherol taken up by the liver with lipoprotein is thought to be resecreted into the plasma in very low density lipoprotein (VLDL). alpha-Tocopherol transfer protein (alphaTTP), which was recently identified as a product of the causative gene for familial isolated vitamin E deficiency, is a cytosolic liver protein and plays an important role in the efficient recycling of plasma vitamin E. To throw light on the mechanism of alphaTTP-mediated alpha-tocopherol transfer in the liver cell, we devised an assay system using the hepatoma cell line McARH7777. Using this system, we found that the secretion of alpha-tocopherol was more efficient in cells expressing alphaTTP than in matched cells lacking alphaTTP. Brefeldin A, which effectively inhibits VLDL secretion by disrupting the Golgi apparatus, had no effect on alpha-tocopherol secretion, indicating that alphaTTP-mediated alpha-tocopherol secretion is not coupled to VLDL secretion. Among other agents tested, only 25-hydroxycholesterol, a modulator of cholesterol metabolism, inhibited alpha-tocopherol secretion. This inhibition is most likely mediated by oxysterol-binding protein. These results suggest that alphaTTP present in the liver cytosol functions to stimulate secretion of cellular alpha-tocopherol into the extracellular medium and that the reaction utilizes a novel non-Golgi-mediated pathway that may be linked to cellular cholesterol metabolism and/or transport.
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PMID:alpha-tocopherol transfer protein stimulates the secretion of alpha-tocopherol from a cultured liver cell line through a brefeldin A-insensitive pathway. 935 67

Chlorinated fatty acids represent a major fraction of extractable, organically bound chlorine in fish. After dietary intake such fatty acids may be transferred from the mother to the foetus through the placenta, and via breast milk to the child. In the present work we have studied the effect of chlorinated oleic acid on the growth of three widely differing types of cells in culture. Chlorinated oleic acid inhibited growth of Human Microvascular Endothelial Cells (HMVEC), Immortilized Human Kidney Epithelial (IHKE) cells, and human Hepatoma cells (HepG2). The order of potency was: HMVEC > IHKE > HepG2. Vitamin E counteracted the inhibitory effect of chlorinated oleic acid on HepG2 cells, but did not significantly affect the fatty acid effect on HMVEC or IHKE. Defatted serum albumin stimulated the growth of HMVEC and IHKE. With HMVEC there was no major interaction between the effect of albumin and chlorinated oleic acid on cell growth. In contrast, with IHKE albumin at low concentration abolished the growth inhibiting effect of chlorinated oleic acid and appreciably counteracted growth inhibition by the fatty acid of HepG2. We conclude that the growth modulation by chlorinated oleic acid and its interaction with vitamin E and albumin are cell specific.
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PMID:Growth modulating effects of chlorinated oleic acid in cell cultures. 976 23

Selenium is essential to human health, and its deficiency is associated with different diseases including liver necrosis. Selenium is protective against viral hepatitis and hepatocellular carcinoma (HCC). The underlying molecular mechanisms of selenium effects are not well known. In this study, in vitro response of HCC-derived cell lines to selenium deficiency is examined alone or in conjunction with Vitamin E and copper/zinc. Here, we show that in vitro selenium deficiency in a subset of HCC-derived cell lines causes oxidative stress and cytochrome c release with subsequent cell death by apoptosis. The oxidative stress and consequent cell death induced by selenium deficiency on these cells are reverted by the antioxidant effect of Vitamin E. However, most HCC cell lines (10 of 13) tolerate selenium deficiency. Consequently, they escape apoptosis. Moreover, nine of these tolerant cell lines have integrated hepatitis B Virus (HBV) DNA in their genomes, and some display p53-249 mutation, indicating past exposure to HBV or aflatoxins, established factors for oxidative stress and cancer risk in liver. An HBV-transfected clone (2.2.15) of the sensitive HepG2 cell line has gained tolerance to selenium deficiency. Our findings indicate that selenium deficiency induces apoptosis in some "hepatocyte-like" cells. However, most HCC cells, particularly HBV-related ones, tolerate selenium deficiency and escape its deadly consequences. Thus, as demonstrated by the gain of survival capacity of apoptosis-sensitive cell lines with Vitamin E, such malignant cells have acquired a selective survival advantage that is prominent under selenium-deficient and oxidative-stress conditions.
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PMID:Acquired tolerance of hepatocellular carcinoma cells to selenium deficiency: a selective survival mechanism? 1458 65

1. Cinnamaldehyde has been shown to be effective in inducing cell apoptosis in a number of human cancer cells. The aim of the present study was to investigate the effect of vitamin E on the apoptotic signalling mechanism induced by cinnamaldehyde in human hepatoma PLC/PRF/5 cells. 2. Using the XTT assay, cinnamaldehyde exhibited a powerful antiproliferative effect on PLC/PRF/5 cells. Apoptosis was elicited when cells were treated with 1 micromol/L cinnamaldehyde, as characterized by the appearance of phosphatidylserine on the outer surface of the plasma membrane. 3. The apoptotic effect induced by cinnamaldehyde could be further supported by the release of cytochrome c, Smac/Diablo and Omi/HtrA2 from mitochondria to the cytosol and activation of caspase 3. Cinnamaldehyde also upregulated the expression of pro-apoptotic protein (Bax) and down-regulated the levels of anti-apoptotic proteins, such as Bcl-2 and the inhibitor of apoptosis protein family (X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein (cIAP)-1 and cIAP-2). 4. Cinnamaldehyde induces the generation of reactive oxygen species (ROS) in cells. Following the pre-incubation of PLC/PRF/5 cells with anti-oxidants, it was found that 100 micromol/L vitamin E significantly diminished the effect of cinnamaldehyde-induced apoptosis, whereas a lesser effect was seen with on 100 micromol/L N-acetyl-L-cysteine. Vitamin E effectively blocked the release of cytochrome c, Smac/Diablo and Omi/HtrA2 from mitochondria to the cytosol in cells treated with cinnamaldehyde. Vitamin E also markedly suppressed caspase 3 activation. The expression of apoptotic inhibitors (XIAP, cIAP-1, cIAP-2) and anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) proteins was affected by vitamin E pretreatment. 5. Taken together, the results suggest that cinnamaldehyde triggers apoptosis possibly through the mitochondrial pathway. Pretreatment with vitamin E markedly prevented cinnamaldehyde-mediated apoptosis, which was associated with the modulation of XIAP, cIAP-1, cIAP-2, Bcl-2 and Bax protein activity.
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PMID:Effects of vitamin E on the cinnamaldehyde-induced apoptotic mechanism in human PLC/PRF/5 cells. 1556 91

The present investigation was carried out to evaluate the antioxidant nature of ethanolic extract of Terminalia arjuna bark (EETA) on N-nitrosodiethylamine (DEN) induced liver cancer in male Wistar albino rats. Liver cancer was induced by single intraperitonial injection of DEN (200 mg/kg). After 2 weeks of DEN administration, Phenobarbital (PB) was given to promote the cancer for up to 14 successive weeks. EETA extract (400 mg/kg) was given post-orally for 28 days to hepatocellular carcinoma-bearing rats. After the experimental period, all the animals were sacrificed and serum, liver and kidney samples were collected for further biochemical analysis. The levels of lipid peroxides (LPO) under basal and also in the presence of inducers (H(2)O(2), ascorbate and FeSO(4)) were estimated in serum, liver and kidney of control and experimental animals. Enzymic antioxidants, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymic antioxidants like Vitamin C (Vit-C) and Vitamin E (Vit-E) levels were determined in all the groups of animals. A significant increase in LPO levels were observed while the levels of enzymic and non-enzymic antioxidants were decreased, when subjected to DEN induction. These altered enzyme levels were ameliorated significantly by administration of EETA at the concentration of 400 mg/kg in drug-treated animals. This protective effect of EETA was associated with inhibition of LPO induced by DEN and to maintain the antioxidant enzyme levels. Our results show an antioxidant activity of T. arjuna bark against DEN-induced liver cancer.
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PMID:Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats. 1632 60


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