Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour- promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat.
High consumption of dietary fat promotes colon carcinogenesis. While this effect is well known the underlying mechanism is not understood. Fatty acid hydroperoxides (LOOH) arise from unsaturated fatty acids in the presence of oxygen and elevated temperature during food processing. An approach was made starting from the assumption that LOOH are present in dietary fats as a result of boiling. LOOH undergoes homolytic cleavage in the presence of iron. We studied their effects on gene expression in colorectal tumour cells using linoleic acid hydroperoxide (LOOH) as model compound. Addition to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide. Both cell lines were observed to increase VEGF and COX-II expression based on mRNA. Expression of VEGF was inhibited by caroverine and ubiquinon.
Nohl
Hans
H
Research Institute of Biochemical Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Austria. hans.nohl@vu-wien.ac.at
Rohr-Udilova
Natalia
N
Gille
Lars
L
Bieberschulte
Werner
W
Jurek
Daniela
D
Marian
Brigitte
B
Schulte-Hermann
Rolf
R
D000236:Adenoma; D002277:Carcinoma; D003110:Colonic Neoplasms; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008041:Linoleic Acids / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000494:pharmacology*; D009930:Organic Chemicals / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000096926:Benzenesulfonamides
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016861:Cyclooxygenase Inhibitors; D004041:Dietary Fats; D008041:Linoleic Acids; D008054:Lipid Peroxides; D009930:Organic Chemicals; D011720:Pyrazoles; D011810:Quinoxalines; D013449:Sulfonamides; D014451:Ubiquinone; D042461:Vascular Endothelial Growth Factor A; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C404729:SC 58560; C467484:VEGFA protein, human; C008285:linoleic acid hydroperoxide; C003741:ubiquinol; C000957:caroverine