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: Jing Wu, Harry Hua Xiang Xia, Shui Ping Tu, Dai Ming Fan, Marie Chia Mi Lin, Hsiang Fu Kung, Shiu Kum Lam, Benjamin Chun Yu Wong
• Journal: Carcinogenesis (Carcinogenesis) Vol. 24 Issue 2 Pg. 243-7 (Feb 2003) ISSN: 0143-3334 [Print] England
• PMID: 12584173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
• Caffeic Acids
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• DNA Primers
• Isoenzymes
• Linoleic Acids
• Pyrazoles
• RNA, Messenger
• Sulfonamides
• 13-hydroxy-9,11-octadecadienoic acid
• Arachidonate 15-Lipoxygenase
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• caffeic acid

Topics

• Apoptosis (drug effects)
• Arachidonate 15-Lipoxygenase (genetics, metabolism)
• Base Sequence
• Caffeic Acids (pharmacology)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• DNA Primers
• Isoenzymes (drug effects)
• Linoleic Acids (pharmacology)
• Prostaglandin-Endoperoxide Synthases (drug effects)
• Pyrazoles (pharmacology)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (enzymology, pathology)
• Sulfonamides (pharmacology)
• Tumor Cells, Cultured