期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：17
页码：9968-9973
DOI：10.1073/pnas.1631086100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Diminished apoptosis, a critical event in tumorigenesis, is linked to down-regulated 15-lipoxygenase-1 (15-LOX-1) expression in colorectal cancer cells. 13-S-hydroxyoctadecadienoic acid (13-S-HODE), which is the primary product of 15-LOX-1 metabolism of linoleic acid, restores apoptosis. Nonsteroidal antiinflammatory drugs (NSAIDs) transcriptionally up-regulate 15-LOX-1 expression to induce apoptosis. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors for linoleic and arachidonic acid metabolites. PPAR-{delta} promotes colonic tumorigenesis. NSAIDs suppress PPAR-{delta} activity in colon cancer cells. The mechanistic relationship between 15-LOX-1 and PPAR-{delta} was previously unknown. Our current study shows that (i) 13-S-HODE binds to PPAR-{delta
