Inhibition of class-3 aldehyde dehydrogenase and cell growth by restored lipid peroxidation in hepatoma cell lines.
Hepatoma cells have a below-normal content of polyunsaturated fatty acids; this reduces lipid peroxidation and the production of cytotoxic and cytostatic aldehydes within the cells. In proportion to the degree of deviation, hepatoma cells also show an increase in the activity of Class-3 aldehyde dehydrogenase, an enzyme important in the metabolism of lipid peroxidation products and also in that of several drugs. When hepatoma cells with different degrees of deviation were enriched with arachidonic acid and stimulated to peroxidize by ascorbate/iron sulphate, their growth rate was reduced in proportion to the quantity of aldehydes produced and to the activity of aldehyde dehydrogenase. Therefore, 7777 cells, less deviated and with low Class-3 aldehyde dehydrogenase activity, were more susceptible to lipid peroxidation products than JM2 cells. It is noteworthy that repeated treatments with prooxidant also caused a decrease in mRNA and activity of Class-3 aldehyde dehydrogenase, contributing to the decreased growth and viability. Thus, Class-3 aldehyde dehydrogenase could be considered relevant for the growth of hepatoma cells, since it defends them against cell growth inhibiting aldehydes derived from lipid peroxidation.
Canuto
R A
RA
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Ospedale S. Luigi, Italy. rosangela.canuto@unito.it
Muzio
G
G
Ferro
M
M
Maggiora
M
M
Federa
R
R
Bassi
A M
AM
Lindahl
R
R
Dianzani
M U
MU
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D016718:Arachidonic Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D016718:Arachidonic Acid; D007770:L-Lactate Dehydrogenase; D000444:Aldehyde Dehydrogenase