Nonsteroidal anti-inflammatory drugs induce apoptosis in esophageal cancercells by restoring 15-lipoxygenase-1 expression

In previous studies, we have found that expression of 15-lipoxygenase-1 (15 -LOX-1) and its main product, 13-S-hydroxyocltadecadienoic acid, are decrea sed in human colorectal cancers and that nonsteroidal anti-inflammatory dru gs (NSAIDs) can therapeutically induce 15-LOX-1 expression to trigger apopt osis in human colorectal cancer cells, NSAIDs similarly induce apoptosis in esophageal cancer cells, although the mechanisms of these effects remain t o be defined. In the present study, we tested whether 15-LOX-1 is down-regu lated in human esophageal cancers using paired normal and tumor human surgi cal samples and whether NSAIDs can up-regulate 15-LOX-1 to restore apoptosi s in esophageal cancer cells. We found that: (a) 15-LOX-1 was down-regulate d in human esophageal carcinomas; (b) NSAIDs induced 15-LOX-1 expression du ring apoptosis in esophageal cancer cells; and (c) 15-LOX-1 inhibition supp ressed NSAID-induced apoptosis, which was restored by 13-S-hydroxyoctadecad ienoic acid but not by its parent compound, linoleic acid. These findings d emonstrate that 15-LOX-1 is down-regulated in human esophageal carcinomas a nd that NSAIDs induce apoptosis in esophageal cancer cells via up-regulatio n of 15-LOX-1. They also support the concept that the loss of the proapopto tic role of 15-LOX-1 in epithelial cancers is not limited to human colorect al cancers.