Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Antineoplastic Agents / pharmacology
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Antioxidants / pharmacology
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Antithrombins / pharmacology
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Apoptosis / drug effects*
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Arachidonate 15-Lipoxygenase / pharmacology*
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Arachidonic Acid / pharmacology
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Blotting, Western
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Caffeic Acids / pharmacology
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Cell Line
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Colonic Neoplasms / enzymology*
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Colonic Neoplasms / pathology*
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Humans
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Hydroxyeicosatetraenoic Acids / biosynthesis
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Isoenzymes / metabolism*
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Linoleic Acid / pharmacology
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Linoleic Acids / pharmacology
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Membrane Proteins
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Nitrobenzenes / pharmacology
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Recombinant Proteins / metabolism
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Sulfonamides / pharmacology
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Sulindac / analogs & derivatives
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Sulindac / pharmacology
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Time Factors
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Tumor Cells, Cultured
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Up-Regulation
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antineoplastic Agents
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Antioxidants
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Antithrombins
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Caffeic Acids
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Hydroxyeicosatetraenoic Acids
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Isoenzymes
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Linoleic Acids
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Membrane Proteins
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Nitrobenzenes
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Recombinant Proteins
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Sulindac
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Arachidonic Acid
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13-hydroxy-9,11-octadecadienoic acid
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Linoleic Acid
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Arachidonate 15-Lipoxygenase
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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sulindac sulfone
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caffeic acid