Inhibition of C6 rat glioma proliferation by [Ru2Cl(Ibp)4] depends on changes in p21, p27, Bax/Bcl2 ratio and mitochondrial membrane potential.

Abstract

The ruthenium compound [Ru(2)Cl(Ibp)(4)] (or RuIbp) has been reported to cause significantly greater inhibition of C6 glioma cell proliferation than the parent HIbp. The present study determined the effects of 0-72h exposure to RuIbp upon C6 cell cycle distribution, mitochondrial membrane potential, reactive species generation and mRNA and protein expression of E2F1, cyclin D1, c-myc, pRb, p21, p27, p53, Ku70, Ku80, Bax, Bcl2, cyclooxygenase 1 and 2 (COX1 and COX2). The most significant changes in mRNA and protein expression were seen for the cyclin-dependent kinase inhibitors p21 and p27 which were both increased (p<0.05). The marked decrease in mitochondrial membrane potential (p<0.01) and modest increase in apoptosis was accompanied by a decrease in anti-apoptotic Bcl2 expression and an increase in pro-apoptotic Bax expression (p<0.05). Interestingly, COX1 expression was increased in response to a significant loss of prostaglandin E(2) production (p<0.001), most likely due to the intracellular action of Ibp. Future studies will investigate the efficacy of this novel ruthenium-ibuprofen complex in human glioma cell lines in vitro and both rat and human glioma cells growing under orthotopic conditions in vivo.

• Authors: Marcel Benadiba, Renata Rolim Prudente Dos Santos, Denise de Oliveira Silva, Alison Colquhoun
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 104 Issue 9 Pg. 928-35 (Sep 2010) ISSN: 1873-3344 [Electronic] United States
• PMID: 20605638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cyclin-Dependent Kinase Inhibitor p21
• Reactive Oxygen Species
• Ruthenium Compounds
• bcl-2-Associated X Protein
• Cyclin-Dependent Kinase Inhibitor p27
• Dinoprostone

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
• Dinoprostone (metabolism)
• Flow Cytometry
• Glioma (drug therapy, metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Rats
• Reactive Oxygen Species (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Ruthenium Compounds (chemistry, pharmacology)
• bcl-2-Associated X Protein (metabolism)