Journal Article

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

Jing Wu, Harry Hua Xiang Xia, Shui Ping Tu, Dai Ming Fan, Marie Chia Mi Lin, Hsiang Fu Kung, Shiu Kum Lam and Benjamin Chun Yu Wong

in Carcinogenesis

Volume 24, issue 2, pages 243-247
Published in print February 2003 | ISSN: 0143-3334
Published online February 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.2.243
15-Lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer

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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.

Keywords: COX, cyclooxygenase; HETE, hydroxyeicosatetraenoic acids; HODE, hydroxyoctadecadienoic acid; 15-LOX, 15-lipoxygenase; NSAIDs, non-steroidal anti-inflammatory drugs.

Journal Article.  3982 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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