Journal
BIOCHEMICAL PHARMACOLOGY
Volume 61, Issue 5, Pages 587-593Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(00)00580-3
Keywords
ajoene; garlic; cyclooxygenase 2; RAW 264.7; macrophage; lipopolysaccharide
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The inducible isoform of cyclooxygenase (COX-2) is implicated in the pathogenesis of various inflammatory diseases as well as in carcinogenesis, especially of gastrointestinal tumors. Epidemiological as well as experimental data support a role for constituents of allium vegetables, such as garlic and onions, in the prevention of gastrointestinal cancer. Therefore, the aim of the present study was to examine whether the garlic-derived natural product ajoene interferes with the COX-2 pathway by using lipopolysaccharide (LPS)-activated RAW 264.7 cells as in vitro model. Ajoene was shown to dose-dependently inhibit the release of LPS (1 mug/mL)-induced prostaglandin E-2 in RAW 264.7 macrophages (IC50 value: 2.3 muM). This effect was found to be due to an inhibition of COX-2 enzyme activity by ajoene (IC50 value: 3.4 muM). Ajoene did not reduce COX-2 expression, but rather increased LPS-induced COX-2 protein and mRNA expression compared to LPS-stimulated cells only. In the absence of LPS, however, ajoene was unable to induce COX-2. The non-steroidal anti-inflammatory drug indomethacin was shown to act similarly in LPS-activated RAW 264.7 cells. These data suggest that ajoene works by a mechanism of action similar to that attributed to non-steroidal anti-inflammatory drugs. This finding may add a novel aspect to the biological profile of the garlic-derived natural product ajoene which might be important for understanding the usefulness of garlic for chemoprevention of gastrointestinal carcinomas. (C) 2001 Elsevier Science Inc. All rights reserved.
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