The metabolite 3-hydroxiglutaric acid effectively reduces glioblastoma growth in vivo by affecting the structural integrity of tumor vasculature.

Abstract

3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.

• Authors: Leticia Oliveira-Ferrer, Jasmin Wellbrock, Melanie Braig, Marianne Klokow, Jessica Hauschild, Carsten Bokemeyer, Walter Fiedler, Suleyman Ergun, Gunter Schuch
• Journal: Cancer letters (Cancer Lett) Vol. 326 Issue 2 Pg. 161-7 (Dec 30 2012) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22902505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 3-hydroxyglutaric acid
• DNA, Complementary
• Glutarates

Topics

• Animals
• Blood Vessels (drug effects)
• Cell Division (drug effects)
• Cell Line, Tumor
• DNA, Complementary
• Glioblastoma (blood supply, pathology)
• Glutarates (pharmacology)
• Humans
• Immunohistochemistry
• Mice
• Mice, Nude
• Neovascularization, Pathologic
• Oligonucleotide Array Sequence Analysis