title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Ru2GLA appears to be a low-toxicity drug and a potential candidate for anti-proliferative therapy of glioma.
authors.affiliation: Department of Cell and Developmental Biology, University of São Paulo, São Paulo, CEP 05508-900, SP, Brazil. alison@usp.br.
authors.forename: Juliano Andreoli
authors.initials: JA
authors.lastname: Miyake
authors.forename: Marcel
authors.initials: M
authors.lastname: Benadiba
authors.forename: Geise
authors.initials: G
authors.lastname: Ribeiro
authors.forename: Denise
authors.initials: D
authors.lastname: DE Oliveira Silva
authors.forename: Alison
authors.initials: A
authors.lastname: Colquhoun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D012428:Ruthenium / Q000008:administration & dosage / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D017965:gamma-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017965:gamma-Linolenic Acid; D012428:Ruthenium
keywords: Glioma; apoptosis; gamma-linolenic acid; proliferation; ruthenium