15-Lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer

• Published in: Carcinogenesis (New York) 2003-02, Vol.24 (2), p.243-247
• Main Authors: Wu, Jing, Xia, Harry Hua Xiang, Tu, Shui Ping, Fan, Dai Ming, Lin, Marie Chia Mi, Kung, Hsiang Fu, Lam, Shiu Kum, Wong, Benjamin Chun Yu
• Format: Article
• Language: English
• Subjects: 15-lipoxygenase; 15-LOX; Antineoplastic agents; Apoptosis - drug effects; Arachidonate 15-Lipoxygenase - genetics; Arachidonate 15-Lipoxygenase - metabolism; Base Sequence; Biological and medical sciences; Caffeic Acids - pharmacology; Chemotherapy; COX; cyclooxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; DNA Primers; HETE; HODE; hydroxyeicosatetraenoic acids; hydroxyoctadecadienoic acid; Isoenzymes - drug effects; Linoleic Acids - pharmacology; Medical sciences; non-steroidal anti-inflammatory drugs; NSAIDs; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - drug effects; Pyrazoles - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Stomach Neoplasms - enzymology; Stomach Neoplasms - pathology; Sulfonamides - pharmacology; Tumor Cells, Cultured
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/24.2.243

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.