Lipid hydroperoxides from processed dietary oils enhance growth of hepatocarcinoma cells.
Linoleic acid, one of the major fatty acid in dietary oils, is an important source for hydroperoxides that may be formed in the presence of oxygen during food processing. Oxidized oils are absorbed in the intestine, transported as chylomicrones to the liver, and may affect unaltered hepatic cells as well as the process of hepatocarcinogenesis. We have studied the effects of linoleic acid hydroperoxides (LOOH) on growth and gene expression of cultured human hepatocellular carcinoma cells (HCC-1.2). The addition of LOOH to the medium of HCC-1.2 carcinoma cells caused dose-dependent cell loss and enhanced lactate dehydrogenase (LDH)-release. Under subtoxic conditions, LOOH induced intracellular hydrogen peroxide production, a decrease of glutathione content, elevated expression of the AP-1 components c-fos and c-jun as well as of the anti-apoptotic enzyme heme oxygenase 1 (HO-1). Furthermore, the cells were pushed by LOOH into the cell cycle as indicated by increased proportion of cells in the S- or G2/M-phase. The unoxidized linoleic acid was not active. Application of SnPPIX, a HO-1 inhibitor, decreased the viability of HCC-1.2 cells, indicating the protective role of HO-1 induction. This is the first evidence that lipid hydroperoxides of dietary origin may be an important driving force for carcinogenesis in the liver.
Rohr-Udilova
Nataliya V
NV
Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. rohr_udilova@yahoo.de
Stolze
Klaus
K
Sagmeister
Sandra
S
Nohl
Hans
H
Schulte-Hermann
Rolf
R
Grasl-Kraupp
Bettina
B
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002452:Cell Count; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004042:Dietary Fats, Unsaturated / Q000032:analysis*; D005511:Food Handling; D005978:Glutathione / Q000032:analysis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism
D004042:Dietary Fats, Unsaturated; D008054:Lipid Peroxides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D005978:Glutathione