The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis

Eur J Pharmacol. 2009 Aug 1;615(1-3):228-33. doi: 10.1016/j.ejphar.2009.04.069. Epub 2009 May 14.

Abstract

We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PC3 and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given -24 and -1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that GIT-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis.

MeSH terms

  • Acetates / pharmacology*
  • Acetates / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Concanavalin A
  • Female
  • Hepatitis, Autoimmune / etiology
  • Hepatitis, Autoimmune / prevention & control*
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Nude
  • Neoplasm Transplantation
  • Nitric Oxide Donors / pharmacology*
  • Nitric Oxide Donors / therapeutic use
  • Oxazoles / pharmacology*
  • Oxazoles / therapeutic use
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Transplantation, Heterologous

Substances

  • 3-phenyl-4,5-dihydro-5-isoxazole acetic acid
  • Acetates
  • Antineoplastic Agents
  • Nitric Oxide Donors
  • Oxazoles
  • Concanavalin A