Lipid A and the lipid A analogue anti-tumour compound ONO-4007 induce nitric oxide synthese in vitro and in vivo

Yoshiyuki Hattori, Csaba Szabo, Steven S. Gross, Christoph Thiemermann, John R. Vane

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The ability of lipid A and the antitumour compound, ONO-4007 (sodium2-deoxy-2-[3S-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-O-(9phenylnonanoyl)-D- glucopyranose 4-sulphate) to induce nitric oxide (NO) synthase was investigated in vitro and in vivo, in comparison to the effects of lipopolysacchride and di-and monophosphoryl lipid A. In J774.2 macrophages, lipopolysaccharide, di-and monophosphoryl lipid A and ONO-4007 (10-9-10-5 g/ml) alone, or in combination with interferion-γ, induced NO synthese (order of potency: lipopolysaccharide > diphosphoryl lipid A > monophosphoryl lipid A > ONO-4007). ONO-4007 increased the activity of the inducible NO synthase in the lung of anesthetised rats (20% of the increase caused by bacterial lipopolysaccharide). Thus, ONO-4007 is a weak inducer of the inducible isoform of NO synthase in vitro and in vivo. The finding that di-and monophosphoryl lipid A also induce NO synthase indicates that the lipid A moiety of lipopolysaccharide contributes to the induction of NO synthase by lipopolysaccharide. The induction of NO synthase by ONO-4007, resulting in the formation of cytotoxic NO may contibute to the antitumour activity of the compound.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume291
Issue number2
DOIs
StatePublished - Oct 15 1995
Externally publishedYes

Fingerprint

Lipid A
Nitric Oxide
Lipopolysaccharides
Nitric Oxide Synthase
Neoplasms
Nitric Oxide Synthase Type II
Sulfates
In Vitro Techniques
ONO 4007
Protein Isoforms
Macrophages
Lung
monophosphoryl lipid A

Keywords

  • Anti-cancer drug
  • Cancer
  • Chemotherapy
  • Cytotoxicity
  • Endotoxin
  • Nitric oxide (NO) synthase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Lipid A and the lipid A analogue anti-tumour compound ONO-4007 induce nitric oxide synthese in vitro and in vivo. / Hattori, Yoshiyuki; Szabo, Csaba; Gross, Steven S.; Thiemermann, Christoph; Vane, John R.

In: European Journal of Pharmacology: Molecular Pharmacology, Vol. 291, No. 2, 15.10.1995, p. 83-90.

Research output: Contribution to journalArticle

Hattori, Yoshiyuki ; Szabo, Csaba ; Gross, Steven S. ; Thiemermann, Christoph ; Vane, John R. / Lipid A and the lipid A analogue anti-tumour compound ONO-4007 induce nitric oxide synthese in vitro and in vivo. In: European Journal of Pharmacology: Molecular Pharmacology. 1995 ; Vol. 291, No. 2. pp. 83-90.
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