US EPA

2723100 

Technical Report 

Discovery and Role of a Novel Eicosanoid Family in Breast Cancer 

Schneider, C 

2007 

NTIS/01470017 

GRA and I 

GRA and I 

There is strong evidence for the induction of the pro-inflammatory enzymes 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in many types of cancer, including breast cancer. Upregula-tion of both enzymes is associated with promoting tumorigenesis and a negative prognosis of the disease. The 5-LOX (leukotriene) and COX-2 (prostaglandin) pathways have traditionally been viewed as independent biosynthetic routes to eicosanoid lipid hormones, yet recent enzy-mological analyses establish that the 5-LOX product, 5-HETE, is an excellent COX-2 substrate, forming a novel double endoperoxide product that has the potential to evolve into a novel family of biomediators. In this funding period we have used LC-MS to detect two cellular metabolites that were derived from the novel di-endoperoxide product. The metabolites are similar in molecular weight to the parent di-endoperoxide, and their formation is blocked by presence of the COX-2 inhibitor indomethacin. Detection of these products is a major step forward in establishing a potential novel eicosanoid-forming pathway resulting from the cross-over of the leukotriene and prostaglandin pathways in breast cancer.