Jurek Daniela, Udilova Natalia, Jozkowicz Alicja, Nohl Hans, Marian Brigitte, Schulte-Hermann Rolf
Institute of Cancer Research, Medical University Vienna, Vienna, Austria.
FASEB J. 2005 Jan;19(1):97-9. doi: 10.1096/fj.04-2111fje. Epub 2004 Nov 2.
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.
在食品加工过程中，不饱和脂肪酸在有氧气和高温的情况下会产生脂肪酸氢过氧化物。在此，我们以亚油酸氢过氧化物（LOOH）作为模型化合物，研究了它们对结肠肿瘤细胞基因表达的影响。将其添加到LT97人腺瘤细胞和SW480人癌细胞的培养基中，会增强细胞内过氧化氢的产生。此外，在这两种细胞系中，均观察到VEGF mRNA和蛋白增加。未氧化的亚油酸几乎没有活性。同时，COX-2表达上调。在LT97细胞中，COX抑制剂SC58560和SC58236完全阻止了VEGF的诱导，这表明该效应依赖于前列腺素合成。已知体内前列腺素介导的VEGF分泌诱导对于腺瘤性息肉的生长及其向癌的进展至关重要。因此，我们的结果首次表明膳食脂质氢过氧化物是结肠癌发生的关键危险因素。
