title: Dietary lipid hydroperoxides induce expression of vascular endothelial growth factor (VEGF) in human colorectal tumor cells.
abstract: Fatty acid hydroperoxides arise from unsaturated fatty acids in the presence of oxygen and elevated temperature during processing of food. Here we have studied their effects on gene expression in colorectal tumor cells using linoleic acid hydroperoxide (LOOH) as a model compound. Its addition to the medium of LT97 human adenoma cells and SW480 human carcinoma cells enhanced the production of intracellular hydrogen peroxide. Furthermore, in both cell lines, increases in VEGF mRNA and protein were observed. Unoxidized linoleic acid had little or no activity. Concomitantly, COX-2 expression was up-regulated. In the LT97 cells, the COX inhibitors SC58560 and SC58236 completely prevented the VEGF induction, suggesting that the effect was dependent on prostaglandin synthesis. In vivo prostaglandin-mediated induction of VEGF secretion is known to be essential for the growth of adenomatous polyps and their progression to carcinomas. Therefore, our results for the first time implicate dietary lipid hydroperoxide as a key risk factor in colon carcinogenesis.
authors.affiliation: Institute of Cancer Research, Medical University Vienna, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Jurek
authors.forename: Natalia
authors.initials: N
authors.lastname: Udilova
authors.forename: Alicja
authors.initials: A
authors.lastname: Jozkowicz
authors.forename: Hans
authors.initials: H
authors.lastname: Nohl
authors.forename: Brigitte
authors.initials: B
authors.lastname: Marian
authors.forename: Rolf
authors.initials: R
authors.lastname: Schulte-Hermann
mesh_terms: D000236:Adenoma / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004041:Dietary Fats / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism* / Q000633:toxicity; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004041:Dietary Fats; D008041:Linoleic Acids; D008054:Lipid Peroxides; D042442:Vascular Endothelial Growth Factors; C008285:linoleic acid hydroperoxide