Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages. Academic Article uri icon

Overview

abstract

  • Taxol, a naturally occurring diterpene with antitumor activity, induces tubulin polymerization to generate abnormally stable and nonfunctional microtubules. Previously, we showed that taxol has lipopolysaccharide (LPS)-like effects on macrophages. As LPS is a potent inducer of macrophage cytokine production, we investigated whether a similar effect is exerted by taxol. In a dose-dependent manner, LPS-free taxol induced release of biologically active tumor necrosis factor alpha (TNF) by inflammatory murine macrophages. Taxol-induced production of TNF was inhibitable by interleukin-10. By Northern blot, taxol (10 and 1 microM) induced TNF mRNA expression to an extent similar to LPS. Induction of TNF mRNA by 10 microM taxol was detectable at 45 min of stimulation, maximal at 90 min, and evident for at least 8 h. The same low concentration of taxol also induced interleukin 1 (IL-1) alpha and beta mRNA expression. We conclude that taxol triggers macrophages for TNF and IL-1 production. These LPS-like effects of taxol might contribute to its antitumor activity.

publication date

  • July 1, 1992

Research

keywords

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Interleukin-1
  • Tumor Necrosis Factor-alpha

Identity

Scopus Document Identifier

  • 0026686641

Digital Object Identifier (DOI)

  • 10.1002/jlb.52.1.119

PubMed ID

  • 1353517

Additional Document Info

volume

  • 52

issue

  • 1