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.
(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.
Norrheim
L
L
Institute of Medical Biochemistry, University of Oslo, Norway.
Sørensen
H
H
Gautvik
K
K
Bremer
J
J
Spydevold
O
O
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013440:Sulfides / Q000494:pharmacology*
D007328:Insulin; D013440:Sulfides; D003907:Dexamethasone; C062078:1-(carboxymethylthio)tetradecane; D010088:Oxidoreductases; D007770:L-Lactate Dehydrogenase; C028427:palmitoyl CoA oxidase; D010170:Palmitoyl-CoA Hydrolase