Sydnone 1: A Mesoionic Compound with Antitumoral and Haematological Effects In Vivo

Basic Clin Pharmacol Toxicol. 2016 Jul;119(1):41-50. doi: 10.1111/bcpt.12545. Epub 2016 Jan 25.

Abstract

This study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd-1) against Walker-256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd-1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro-apoptotic protein expression (Bax and p53), while the expression of the anti-apoptotic protein Bcl-2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd-1 treatment. However, significant splenomegaly was evident in animals that received Syd-1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd-1 against Walker-256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma 256, Walker / drug therapy*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cell Line, Tumor
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Spleen / drug effects
  • Spleen / pathology
  • Superoxide Dismutase / metabolism
  • Sydnones / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Bax protein, rat
  • Sydnones
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Catalase
  • Peroxidase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Transferase
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione