title: 15-Lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer.
abstract: It has been found that expression of 15-lipoxygenase-1 (15-LOX-1) and its main product, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), are decreased in human colorectal and esophageal cancers and that non-steroidal anti-inflammatory drugs (NSAIDs) can therapeutically induce 15-LOX-1 expression to trigger apoptosis in those cancer cells. We found that a specific cyclooxygenase-2 (COX-2) inhibitor SC-236 similarly induced apoptosis in gastric cancer cells. In the present study, we tested whether SC-236 induced apoptosis through up-regulation of 15-LOX-1 in gastric cancer. We found that: (i) SC-236 inhibited growth of gastric cancer cells mainly by inducing apoptosis; (ii) SC-236 induced 15-LOX-1 expression and increased endogenous 13-S-HODE product, instead of 15-S-HETE during apoptosis; (iii) SC-236 did not affect expression of COX-1, COX-2, 5-LOX and 12-LOX; and (iv) 15-LOX-1 inhibition suppressed SC-236 induced apoptosis. These findings demonstrated that SC-236 induced apoptosis in gastric cancer cells via up-regulation of 15-LOX-1, and 13-S-HODE. These are potential and new targets for prevention and treatment of gastric cancer.
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Harry Hua Xiang
authors.initials: HH
authors.lastname: Xia
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Tu
authors.forename: Dai Ming
authors.initials: DM
authors.lastname: Fan
authors.forename: Marie Chia Mi
authors.initials: MC
authors.lastname: Lin
authors.forename: Hsiang Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Shiu Kum
authors.initials: SK
authors.lastname: Lam
authors.forename: Benjamin Chun Yu
authors.initials: BC
authors.lastname: Wong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002109:Caffeic Acids / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D007527:Isoenzymes / Q000187:drug effects*; D008041:Linoleic Acids / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000096926:Benzenesulfonamides
chemical_list: D001093:Arachidonate 15-Lipoxygenase; D002109:Caffeic Acids; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D007527:Isoenzymes; D008041:Linoleic Acids; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C024348:13-hydroxy-9,11-octadecadienoic acid; C040048:caffeic acid