15-Lipoxygenase-1 mediates nonsteroidal anti-inflammatory drug-induced apoptosis independently of cyclooxygenase-2 in colon cancer cells.
We previously found (I. Shureiqi et al., Carcinogenesis (Lond.), 20: 1985-1995, 1999; I. Shureiqi et al, J. Natl. Cancer Inst., 92: 1136-1142, 2000) that (a) 15-lipoxygenase-1 (15-LOX-1) protein and its product 13-S-hydroxyoctadecadienoic acid (13-S-HODE) are decreased; and (b) nonsteroidal anti-inflammatory drug (NSAID)-induced 15-LOX-1 expression is critical to NSAID-induced apoptosis in colorectal cancer cells expressing cyclooxygenase-2 (COX-2). We used the NSAIDs sulindac sulfone (COX-2-independent) and NS-398 (a COX-2 inhibitor) to assess NSAID upregulation of 15-LOX-1 in relation to COX-2 inhibition during NSAID-induced apoptosis in the DLD-1 (COX-2-negative) colon cancer cell line. We found that: (a) NSAIDs up-regulated 15-LOX-1, which preceded apoptosis; and (b) 15-LOX-1 inhibition blocked NSAID-induced apoptosis, which was restored by 13-S-HODE but not by its parent, linoleic acid. NSAIDs can induce apoptosis in colon cancer cells via up-regulation of 15-LOX-1 in the absence of COX-2.
Shureiqi
I
I
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston 77030-4095, USA.
Chen
D
D
Lotan
R
R
Yang
P
P
Newman
R A
RA
Fischer
S M
SM
Lippman
S M
SM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001093:Arachidonate 15-Lipoxygenase / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism*; D019787:Linoleic Acid / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013467:Sulindac / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000975:Antioxidants; D000991:Antithrombins; D002109:Caffeic Acids; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D008041:Linoleic Acids; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011994:Recombinant Proteins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D013467:Sulindac; D016718:Arachidonic Acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D001093:Arachidonate 15-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C025463:sulindac sulfone; C040048:caffeic acid