Thalidomide and Its Analogues Inhibit Lipopolysaccharide-mediated Induction of Cyclooxygenase-2

We investigated the effect of thalidomide, a compound with immunomodulatory and antiangiogenic properties, on lipopolysaccharide (LPS)-mediated induction of cyclooxygenase-2 (Cox-2) and prostaglandin (PG) biosynthesis in murine macrophages. Thalidomide caused a dose-dependent inhibition of LPS-media...

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Bibliographic Details
Published in:Clinical cancer research 2001-11, Vol.7 (11), p.3349-3355
Main Authors: FUJITA, Junya, MESTRE, Juan R, ZELDIS, Jerome B, SUBBARAMAIAH, Kotha, DANNENBERG, Andrew J
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Medical sciences
Pharmacology. Drug treatments
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Summary:We investigated the effect of thalidomide, a compound with immunomodulatory and antiangiogenic properties, on lipopolysaccharide (LPS)-mediated induction of cyclooxygenase-2 (Cox-2) and prostaglandin (PG) biosynthesis in murine macrophages. Thalidomide caused a dose-dependent inhibition of LPS-mediated induction of PGE 2 synthesis in RAW 264.7 cells. The induction of Cox-2 protein and mRNA by LPS was also suppressed by thalidomide. Based on the results of nuclear run-off assays and transient transfections, treatment with LPS stimulated Cox-2 transcription, an effect that was unaffected by thalidomide. Thalidomide decreased the stability of Cox-2 mRNA. A series of structural analogues of thalidomide also inhibited LPS-mediated induction of Cox-2 and PGE 2 synthesis. Taken together, these data provide new insights into the antineoplastic and anti-inflammatory properties of thalidomide.
ISSN:1078-0432
1557-3265