Suppression of tumour-promoting factors in fat-induced colon carcinogenesis by the antioxidants caroverine and ubiquinone.
Fatty acid hydroperoxides are produced from unsaturated fatty acids in the presence of oxygen at elevated temperatures during food processing. Their effects on gene expression in colorectal tumour cells were studied using linoleic acid hydroperoxide (LOOH) as a model compound. Addition of LOOH to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide. Both cell lines were observed to increase VEGF factors based on mRNA. High consumption of dietary fat promotes colon carcinogenesis in the long-term. While this effect is well known, the underlying mechanisms are not understood. An approach was made starting from the assumption that LOOH is present in dietary fats as a result of heating. LOOH undergoes homolytic cleavage in the presence of iron. Various radicals are formed on mixing LT97 or SW480 cells with LOOH. The expression of tumour-promoting factors was inhibited by caroverine and ubiquinone, which may be justified as active chemopreventive agents.
Nohl
Hans
H
Research Institute of Biochemical Pharmacology and Toxicology, University of Veterinary Medicine Vienna, A-1210 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-Herman
Rolf
R
D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000378:metabolism; D008041:Linoleic Acids / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D008054:Lipid Peroxides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D011810:Quinoxalines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014451:Ubiquinone / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004041:Dietary Fats; D008041:Linoleic Acids; D008054:Lipid Peroxides; D011810:Quinoxalines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014451:Ubiquinone; C008285:linoleic acid hydroperoxide; D017665:Hydroxyl Radical; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; C000957:caroverine