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Topoisomerase inhibitors as anti-arthritic agents

J K Jackson1, T Higo, W L Hunter

  • 1Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|February 28, 2008
PubMed
Abstract

Insights

Certain anticancer drugs, specifically topoisomerase inhibitors, show promise in treating rheumatoid arthritis (RA). These agents effectively target key RA disease processes like inflammation and cell proliferation, suggesting a new therapeutic avenue for RA patients.

Area of Science:

  • Rheumatology
  • Oncology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) involves inflammation, synoviocyte proliferation, angiogenesis, and matrix metalloproteinase degradation.
  • Anticancer agents targeting topoisomerases are explored for their potential in managing RA pathophysiology.

Purpose of the Study:

  • To investigate structurally diverse anticancer topoisomerase inhibitors.
  • To assess their efficacy in inhibiting RA-associated disease processes.

Main Methods:

  • Tested topoisomerase I (camptothecin, beta-laperchone) and II (etoposide, doxorubicin, plumbagin, menadione) inhibitors.
  • Assessed neutrophil activation, synoviocyte proliferation, angiogenesis, and matrix metalloproteinase expression.

Main Results:

  • All agents inhibited synoviocyte proliferation; camptothecin showed broad inhibition at nanomolar concentrations.
  • Plumbagin and menadione inhibited neutrophil activation, angiogenesis, and collagenase expression.
  • Other agents demonstrated varying degrees of inhibition on angiogenesis and collagenase expression.

Conclusions:

  • Topoisomerase I and II inhibitors, particularly camptothecin, show potential as therapeutic agents for rheumatoid arthritis.
  • These findings support further investigation of these agents in RA treatment.

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