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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Tumor cell-specific inhibition of inducible nitric oxide synthase activation by tiazofurin

T Samardzic1, S Stosic-Grujicic, N Raicevic

  • 1Institute for Biological Research Sinisa Stankovic, Belgrade, Yugoslavia.

International Immunopharmacology
|May 19, 2001
PubMed

Insights

Tiazofurin (TR) inhibits L929 fibrosarcoma cell growth and nitric oxide (NO) production by decreasing inducible NO synthase (iNOS) mRNA expression. This effect appears tumor-selective, as murine embryonic fibroblasts were resistant to TR.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Nitric oxide (NO) plays a crucial role in various physiological and pathological processes.
  • Inducible NO synthase (iNOS) is a key enzyme in NO production, often upregulated in cancer.
  • Tiazofurin (TR) is an investigational antineoplastic agent with known effects on cell proliferation.

Purpose of the Study:

  • To investigate the effects of tiazofurin (TR) on cell proliferation.
  • To determine the impact of TR on cytokine-induced nitric oxide (NO) production.
  • To explore the potential tumor-selective action of TR.

Main Methods:

  • Cell culture of L929 fibrosarcoma cells and murine embryonic fibroblasts.
  • Treatment with varying concentrations of tiazofurin (TR).
  • Assessment of cell viability, proliferation, and inducible NO synthase (iNOS) mRNA expression using techniques like RT-PCR, and measurement of NO production.

Main Results:

  • Tiazofurin (TR) inhibited the proliferation of nonconfluent L929 cells in a dose-dependent manner.
  • TR significantly decreased interferon-gamma (IFN-gamma) + lipopolysaccharide (LPS)-induced iNOS mRNA expression and NO production in confluent L929 cells, without affecting cell viability.
  • TR did not inhibit IFN-gamma-induced IRF-1 mRNA expression, suggesting an intracellular pathway downstream of IRF-1 is affected.
  • Murine embryonic fibroblasts showed resistance to TR-mediated inhibition of iNOS induction, indicating potential tumor selectivity.

Conclusions:

  • Tiazofurin (TR) exhibits anti-proliferative effects on L929 fibrosarcoma cells.
  • TR effectively suppresses inducible nitric oxide synthase (iNOS) expression and subsequent NO production in L929 cells, independent of IRF-1.
  • The observed resistance of murine embryonic fibroblasts to TR suggests a potential for tumor-selective therapeutic application of tiazofurin.

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