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)

(1) The relation between the effects of the sulfur-substituted fatty acid analogue, tetradecylthioacetic acid (TTA), dexamethasone and insulin on enzyme induction and growth rate was studied in Morris hepatoma 7800 C1 cells in culture. (2) The activities of the cynanide-insensitive palmitoyl-CoA oxidase and palmitoyl-CoA hydrolase were induced about 2-fold by 50 microM TTA after 72 h of treatment. Catalase was less induced and NADPH-cytochrome-c2 reductase, glucose-6-phosphate dehydrogenase and lactate dehydrogenase were unaffected by the fatty acid analogue. (3) Dexamethasone (250 nM) induced the same enzymes as did TTA, but was a less efficient than 50 microM TTA. However, in combination their effects were more than additive, resulting in 4-7-fold increases. (4) Insulin (400 nM) counteracted the inductive effects of both TTA and dexamethasone on all enzymes except for lactate dehydrogenase, which was induced by the combination of all three compounds. (5) TTA inhibited the growth rate of the cells, and this effect was potentiated by dexamethasone and counteracted by insulin. (6) The enzyme inductions were similar in exponential and plateau phases of growth, indicating that these processes were independently affected by the three compounds.
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PMID:Synergistic actions of tetradecylthioacetic acid (TTA) and dexamethasone on induction of the peroxisomal beta-oxidation and on growth inhibition of Morris hepatoma cells. Both effects are counteracted by insulin. 196 66

(1) The activities of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase in Morris hepatoma 7800 C1 cells were studied. The cells were grown until they reached steady state (constant DNA content per dish) and then were cultured in the presence of fatty acids or alkylthioacetic acids, i.e., S-substituted fatty acid analogues. (2) The fatty acid analogues increased the activity of the cyanide-insensitive palmitoyl-CoA oxidase several-fold. The effect was dose-dependent; 5 microM tetradecylthioacetic acid (TTA) was sufficient to give a significant induction. With 20 microM TTA, the increase in enzyme activity was discernable after 3 h and reached a maximum after 3 days. The inducing effect of the alkylthioacetic acids increased with the length of the hydrophobic alkyl end of the analogue. The inducing ability disappeared when the fatty acid analogue was omega-oxidized to the corresponding dicarboxylic acid. Oxidation of the sulfur atom resulted in inhibited cellular uptake and abolished enzyme induction. (3) At higher concentrations (0.5-1 mM), normal fatty acids also induced cyanide-insensitive palmitoyl-CoA oxidation. Myristic acid was the most potent inducer, whereas fatty acids with shorter as well as longer carbon chains were less efficient. The inducing effect increased with the number of double bounds in the fatty acid. (4) The normal fatty acids as well as the fatty acid analogues also induced palmitoyl-CoA hydrolase, but the relative changes were much less pronounced than with the palmitoyl-CoA oxidase.
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PMID:Induction of peroxisomal beta-oxidation in 7800 C1 Morris hepatoma cells in steady state by fatty acids and fatty acid analogues. 271 97