Novel ruthenium - gamma-linolenic acid complex inhibits C6 rat glioma cell proliferation in vitro and in the orthotopic C6 model in vivo after osmotic pump infusion

Anticancer Res. 2014 Apr;34(4):1901-11.

Abstract

Aim: Gliomas are primary brain tumours. Gamma-linolenic acid (GLA) exerts anti-proliferative effects. Several ruthenium-containing complexes have antiproliferative effects and can be used as adjuvant therapies in cisplatin-resistant cancer. The present study reports on the anti-proliferative properties and effects on tumour morphology of a novel diruthenium-GLA complex (Ru2GLA) and its comparison with GLA in the C6 rat glioma model both in vitro and in vivo.

Materials and methods: In vitro and in vivo experiments were performed on C6 glioma rat cells, and in an orthotopic model.

Results: Ru2GLA (100 μM) appears to be an inhibitor of C6 rat glioma cell proliferation. The nuclear area of Ru2GLA-treated cells was 2.18-times larger than that of control cells, suggesting DNA replication occurred but mitosis was blocked in the G2-M phase. Ru2GLA (2 mM) inhibited C6 cell proliferation in vivo and the changes in tumor morphology confirm both cellular uptake and collagen fibre-binding in the extracellular matrix.

Conclusion: Ru2GLA appears to be a low-toxicity drug and a potential candidate for anti-proliferative therapy of glioma.

Keywords: Glioma; apoptosis; gamma-linolenic acid; proliferation; ruthenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Female
  • Glioma / drug therapy
  • Glioma / pathology*
  • Glioma / ultrastructure
  • Rats
  • Ruthenium / administration & dosage
  • Ruthenium / pharmacology*
  • Tumor Burden / drug effects
  • gamma-Linolenic Acid / administration & dosage
  • gamma-Linolenic Acid / pharmacology*

Substances

  • gamma-Linolenic Acid
  • Ruthenium