Thalidomide and its analogues inhibit lipopolysaccharide-mediated Iinduction of cyclooxygenase-2

Clin Cancer Res. 2001 Nov;7(11):3349-55.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Line
  • Cyclooxygenase 2
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Immunoblotting
  • Isoenzymes / drug effects*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lipopolysaccharides / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA Stability / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thalidomide / analogs & derivatives
  • Thalidomide / pharmacology*

Substances

  • Isoenzymes
  • Lipopolysaccharides
  • RNA, Messenger
  • Thalidomide
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases