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)

Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60 microM DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution titers of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl 38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSO4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60 microM of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation.
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PMID:Inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine. 171 97

Oxidants are suspected to represent important human carcinogens. They are mutagenic and may participate in the activation of proto-oncogenes and the inactivation of tumor suppressor genes. We have studied the capacity of hydrogen peroxide plus ferric chloride (FeCl3) to induce base pair changes in the hotspot codons 248 and 249 of the p53 tumor suppressor gene in human fibroblasts. In codon 248 (CGG) H2O2/FeCl3 only induced the transversion of G to C in the second position and the transition of G to A in the third position. No evidence was obtained for spontaneous or oxidant-induced deamination of 5-methylcytosine in the CpG dinucleotide of codon 248 since neither C to T transitions in the first position nor G to A transitions in the middle position were observed. H2O2/FeCl3 efficiently induced G to T transversions at both G-residues of codon 249 (AGG) and C to A transversions at the first position of codon 250 (CCC). It is evident that H2O2/FeCl3 possesses essentially the same mutagenic specificity for codons 249 and 250 of p53 as bulky carcinogens such as aflatoxin B1, benzo(a)pyrene or heterocyclic amines. In particular, it is not possible to eliminate oxidants from the list of candidate carcinogens which may be responsible for the high incidence of p53 codon 249 AGT mutations in hepatocellular carcinoma from certain areas of the world.
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PMID:Oxy-radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene. 803 11

Deferoxamine is commonly used for treatment of iron intoxication. Because the usual dose is unable to chelate sufficient iron before severe injury occurs, "high-dose" deferoxamine treatment has been proposed. However, several authors have reported severe toxicity after deferoxamine therapy. Although the hemodynamic effects are well described, the cellular toxicity of deferoxamine is unknown. Accordingly, we investigated the cellular toxicity of deferoxamine using in vitro techniques in two cell lines. Brain cells were harvested from fetal rats and cultured for 14-21 days before deferoxamine exposure. Using similar techniques, rat hepatoma cells were grown until confluent. Deferoxamine was added to the cultures to achieve final concentrations of 200-800 microg/ml, corresponding to in vivo infusion rates of 15-60 mg/kg/h. Deferoxamine was removed after 3 or 6 days by changing the medium. Subtoxic FeCl3 (500 mg/dl) was concurrently added to identical cultures to determine if deferoxamine potentiated iron toxicity. Cell viability was measured by a colorimetric assay. The addition of deferoxamine (0.2, 0.4, 0.8 mg/ml) significantly decreased cell viability in both cell groups. The effect of deferoxamine on primary cortical brain cultures was similar for the three concentrations used, and was similar when examined either 72 h or 6 days later. In contrast, hepatoma cell cultures evidenced a dose- dependent cell loss that increased with the length of exposure. The addition ofsubtoxic amounts of FeCl3 (500 microg/dl) in the presence of deferoxamine was protective in all cultures, and abolished deferoxamine-induced cell loss. Interestingly, the addition of serum albumin significantly reduced the amount of iron present in cells, suggesting its potential use to treat iron toxicity. These results suggest that deferoxamine, in the absence of iron, is toxic to cortical brain and hepatoma cells in vitro.
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PMID:Deferoxamine toxicity in hepatoma and primary rat cortical brain cultures. 1153 Aug 35

Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55) increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions.
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PMID:Sugars increase non-heme iron bioavailability in human epithelial intestinal and liver cells. 2434 76